Stockwinners Market Radar for September 15, 2024 - Earnings, Upgrades downgrades, option trades, Best Stock Advisory Service

20:07 EDT Fly Intel: Top five weekend stock stories - Catch up on the weekend's top five stories with this list compiled by The Fly: 1. DirecTV (T; TPG) and Disney (DIS) announced an agreement in principle that provides "greater choice, value, and flexibility to their mutual customers," the companies said. As a result, Disney's full linear suite of networks has been restored to DirecTV, DirecTV STREAM and U-verse customers while both parties work to finalize a new, multi-year contract. Among the core points agreed to are: Continued carriage at market-based terms of Disney's entertainment, sports and news programming from its comprehensive linear portfolio, which includes the ABC Owned Television Stations, the ESPN networks, the Disney-branded channels, Freeform, the FX networks and the National Geographic channels. 2. Alcoa (AA) announced that it has entered into a binding share purchase and subscription agreement with Saudi Arabian Mining Company, or Ma'aden, under which Alcoa will sell its full ownership interest of 25.1% in the Ma'aden Joint Venture to Ma'aden for approximately $1.1 billion. The transaction consideration comprises approximately 86M shares of Ma'aden -- valued at $950M based on the volume-weighted average share price of Ma'aden for the last 30 calendar days as of September 12, 2024 - and $150M in cash. 3. Schlumberger (SLB) was the Nvidia (NVDA) of the 1980s-and the beaten-down stock could still produce some Nvidia-like gains, Andrew Bary writes in this week's edition of Barron's. Schlumberger, now called SLB, was one of the market's hottest stocks as the leading servicer to the then-dominant energy industry, and at one point had the world's fifth-largest market cap. SLB is still the world's leading oil-services company, with operations in 100 countries, but energy matters little in the S&P 500 index, and the out-of-favor stock isn't trading much higher than it did 40 years ago, the author notes, arguing, however, that SLB is worth a fresh look. 4. Tim Burton's sequel "Beetlejuice Beetlejuice" stayed atop the North American box office with $51.6M as it moved towards the $200M mark domestically. Overseas, the Warner Bros.' (WBD) movie grossed an estimated $28.7M for a foreign cume of $76.3M and $364.3M globally. The film received a B+ CinemaScore and sports a Rotten Tomatoes critics score of 76%. 5. Palantir (PLTR) saw a positive mention in this week's edition of Barron's.

10:02 EDT Replimune presents primary analysis data from IGNYTE clinical trial - Replimune Group announced that data from the primary analysis of the IGNYTE clinical trial of RP1 combined with nivolumab were presented as a late breaking abstract during an oral session at the European Society for Medical Oncology Congress 2024 in Barcelona. The anti-PD1 failed melanoma cohort from the IGNYTE clinical trial included 140 patients who received RP1 plus nivolumab after confirmed progression while being treated for at least 8 weeks with anti-PD1 based therapy. The primary analysis by blinded independent central review was triggered once all patients had been followed for at least 12 months. Because of requirements that patients must have confirmed progressive disease on an immediate anti-PD1-based therapy, which is the current first line standard of care, most of the patients enrolled had 1 or 2 lines of prior therapies. The overall response rate was 33.6% by modified RECIST 1.1 criteria, the primary endpoint as defined in the protocol, and 32.9% by RECIST 1.1 criteria, an additional sensitivity analysis requested by the FDA. The complete response rate by mRECIST was 15%. In patients who had prior anti-PD1 and anti-CTLA-4, the ORR was 27.7% and for those who had primary resistance to anti-PD1, the ORR was 35.9% by mRECIST. Median duration of response from response initiation was 21.6 months and media duration of response from treatment initiation was 27.6 months. At the time of the analysis, 85% of responses were ongoing more than a year from starting treatment. While median overall survival has not been reached, one-, two- and three-year survival rates were 75.3%, 63.3% and 54.8% respectively. RP1 combined with nivolumab continues to be well-tolerated. Treatment-related adverse events associated with RP1 in combination with nivolumab were predominantly Grade 1-2 constitutional type events, with a low incidence of Grade 3-4 events, which were predominantly Grade 3. Grade 4 events were one each of lipase increased, cytokine release syndrome, myocarditis, hepatic cytolysis and splenic rupture. There were no Grade 5 events.

09:55 EDT Bristol Myers presents landmark 10-year follow-up data from CheckMate -067 - Bristol Myers announced 10-year follow-up data from CheckMate -067, a randomized, double-blind, Phase 3 clinical trial, which showed continued durable improvement in survival with first-line Opdivo plus Yervoy therapy and Opdivo monotherapy, versus Yervoy alone, in patients with previously untreated advanced or metastatic melanoma. With a minimum follow up of 10 years, median overall survival was 71.9 months with Opdivo plus Yervoy - the longest reported median OS in a Phase 3 advanced melanoma trial - 36.9 months with Opdivo and 19.9 months with Yervoy. Among all randomized patients in the trial, 64% of patients who received the combination, 50% of Opdivo-treated patients and 33% of Yervoy-treated patients did not receive subsequent systemic therapy at the 10-year follow up mark. In addition, at 10 years of follow up, the Opdivo plus Yervoy combination showed melanoma-specific survival rates of 52% compared to 44% and 23% among patients treated with Opdivo alone and Yervoy alone, respectively. Durable, sustained clinical benefit was also observed with Opdivo plus Yervoy or Opdivo alone across relevant subgroups, including in patients with BRAF mutation and wild-type tumors. Among patients with BRAF-mutant tumors, the rate of OS at 10 years was 52% in patients who received Opdivo plus Yervoy, 37% for Opdivo alone, and 25% for Yervoy alone. In patients with BRAF wild-type tumors, the rate of OS at 10 years was 39% in patients who received Opdivo plus Yervoy, 37% for Opdivo alone and 17% for Yervoy alone. At 10 years of follow up, the objective response rate was higher for the two Opdivo groups, in combination with Yervoy and alone, at 58.3% and 44.9%, respectively than the Yervoy group at 19.0%. The median duration of response was not reached for those who received Opdivo plus Yervoy, while the median DoR was 103.2 months for Opdivo-treated patients and 19.2 months for Yervoy-treated patients. The safety profile for Opdivo plus Yervoy was consistent with prior findings, with no new safety signals observed and no additional treatment-related deaths occurring since the prior three analyses. Grade 3/4 treatment-related adverse events were reported in 62.6% of patients in the combination group, 24.6% of patients in the Opdivo group, and 29.6% of patients in the Yervoy group.

09:38 EDT Exelixis presents final overall survival results from Phase 3 CONTACT-02 study - Exelixis announced detailed final overall survival results from CONTACT-02, a phase 3 pivotal study evaluating cabozantinib in combination with atezolizumab compared with a second novel hormonal therapy in patients with metastatic castration-resistant prostate cancer and measurable extra-pelvic soft tissue disease who have progressed on one prior NHT. The two primary endpoints for CONTACT-02 were progression-free survival and OS. At a median follow-up of 24.0 months, the final analysis of OS showed a numerical but not statistically significant improvement favoring cabozantinib in combination with atezolizumab. An improvement in OS was observed in multiple clinical subgroups, notably in patients with bone or liver metastases, with the latter category representing a population whose disease may be evolving away from androgen receptor signaling. Treatment-related grade 3-4 adverse events occurred in 40% of patients receiving cabozantinib in combination with atezolizumab and 8% of those receiving NHT. Treatment-related AEs leading to discontinuation of all treatment components were similar. The time to clinically meaningful deterioration in quality of life was similar between arms, and the combination of cabozantinib and atezolizumab did not impair quality of life relative to generally well-tolerated NHT. As previously announced, CONTACT-02 met one of its two primary endpoints, demonstrating a statistically significant benefit in PFS in the predefined PFS ITT population.

09:29 EDT Veracyte announces new data from Phase 3 STAMPEDE clinical trial - Veracyte announced that new data from a phase 3 trial of the multi-center, randomized STAMPEDE clinical trial show that its Decipher Prostate Genomic Classifier is prognostic for clinical outcomes and predicts benefit from docetaxel in patients with metastatic prostate cancer. The findings were presented at the European Society for Medical Oncology 2024 Congress in Barcelona. These findings support Veracyte's plan to expand use of the Decipher Prostate test - currently widely used to guide care for localized prostate cancer - to patients with metastatic disease. Prostate cancer accounts for a fifth of all male cancer-related deaths globally and the number is expected to double over the next two decades. In the United States, it is the second-leading cause of cancer deaths among men, with more than 35,000 men expected to die of the disease in 2025.2 Most prostate cancer deaths occur in patients who first presented with advanced or metastatic disease. In the new study, researchers analyzed data for 1,523 patients with advanced or metastatic prostate cancer who were followed in the STAMPEDE trial for a median of 14 years. They found that higher Decipher Prostate test scores were associated with an increased risk of death in both groups. Additionally, among the 832 patients with metastatic disease, only those with higher Decipher Prostate scores received a significant survival benefit from the addition of docetaxel to ADT. These patients had a 36% reduction in risk of death with the addition of docetaxel as compared to those with lower Decipher scores who did not significantly benefit. Notably, docetaxel was beneficial in patients with higher Decipher Prostate scores regardless of whether they had high- or low-volume prostate cancer. This is important because current clinical practice favors use of docetaxel in patients with high- but not low-volume disease. Veracyte expects to begin offering the Decipher Prostate test to patients with metastatic prostate cancer in early 2025, after its anticipated reimbursement by Medicare. MolDX, a program that establishes Medicare coverage for advanced molecular diagnostic tests, recently issued a local coverage determination for molecular testing in patients with metastatic prostate cancer, providing what Veracyte believes is a pathway to coverage for its test.

09:15 EDT MacroGenics announces updated efficacy, safety data from TAMARACK Phase 2 study - MacroGenics presented updated efficacy and safety results from the TAMARACK Phase 2 study of vobramitamab duocarmazine, an antibody-drug conjugate that targets B7-H3, for patients with metastatic castration-resistant prostate cancer. The data were featured in a poster presentation at the European Society for Medical Oncology Congress, taking place in Barcelona, Spain from September 13-17, 2024. The abstract submitted to ESMO was based on a data cut-off as of April 12, 2024; updated data based on a cut-off date of July 9, 2024. The TAMARACK trial enrolled a total of 181 participants, with 176 participants receiving at least one dose of vobra duo at either 2.0 mg/kg q4W or 2.7 mg/kg q4W. As of the data cut-off date, 23 and 16 participants remained on treatment in the 2.0 mg/kg and 2.7 mg/kg cohorts, respectively. While mCRPC study participants are no longer being dosed in the study, participants continue to be monitored for adverse events, disease progression, and survival. Overall, the company believes that the results to date from the TAMARACK study indicate antitumor activity associated with vobra duo in mCRPC as demonstrated by the protocol-specified primary endpoint of landmark 6-month radiographic progression-free survival rate, as well as other measures of tumor response. In the intent-to-treat population, 6-month rPFS rate was 69% for the 2.0 mg/kg arm and 70% for the 2.7 mg/kg arm. Landmark 6-month rPFS rates were consistent across taxane-naive study participants and taxane pre-treated study participants, regardless of treatment arm. Although immature, with only 65 PFS events as of the data cut-off, median rPFS was approximately 8.5 months for the 2.0 mg/kg cohort and 7.5 months for the 2.7 mg/kg cohort. Because these results were immature as of the cutoff date, they are likely to change as additional events accrue. Out of 45 RECIST-response evaluable patients in the 2.0 mg/kg arm, the confirmed objective response rate was 20.0% and the unconfirmed ORR was 26.7%. Out of 32 RECIST-response evaluable patients in the 2.7 mg/kg arm, the confirmed ORR was 40.6% and the unconfirmed ORR was 46.9%. Confirmed ORR was comparable between taxane-naive study participants and taxane pre-treated study participants, regardless of treatment arm. Tumor responses did not appear to correlate with baseline B7-H3 expression based on archival tissue samples of mixed age. In the 2.0 mg/kg cohort, 65.6% of study participants experienced a Grade greater than or equal to 3 treatment-emergent AE; this cohort had a discontinuation rate of 25.6% and a dose reduction rate of 50.0% due to TEAEs. In the 2.7 mg/kg cohort, 62.8% of study participants experienced a Grade greater than or equal to 3 TEAE; this cohort had a discontinuation rate of 38.4% and a dose reduction rate of 54.7% due to TEAEs. The majority of TEAEs with a greater than or equal to 10% incidence rate in either treatment arm was limited to Grade 1/2 events. Eight fatal treatment-related AEs as assessed by the treating physician: five in the 2.0 mg/kg cohort and three in the 2.7mg/kg cohort. These include three events of pneumonitis, and one event each of cardiac failure, stress cardiomyopathy, ventricular fibrillation, pleural effusion, and gastrointestinal hemorrhage. Rates of treatment-related AEs and treatment-related severe AEs were similar between taxane-naive and taxane pre-treated study participants. In the 2.0 mg/kg cohort, 25.6% of study participants remained on study drug as of July 9, 2024. Study participants received a median number of 6 doses, with a median dose intensity of 92.6%. In the 2.7 mg/kg cohort, 18.6% of study participants remained on study drug as of the data cut-off date. Study participants received a median number of 6 doses, with a median dose intensity of 81.7%. Taxane-naive study participants experienced higher rates of dose reductions due to TEAEs and dose interruptions due to TEAEs compared to taxane pre-treated study participants.

09:06 EDT 23andMe announces in vivo results for 23ME-01473 in Phase 1 trial - 23andMe announced nonclinical data supporting the anti-tumor activity of its first-in-class 23ME-01473 antibody targeting the NKG2D ligand ULBP6 at the European Society of Medical Oncology Congress 2024 in Barcelona, September 13-17. In a poster presentation at the 2024 ESMO Congress, 23andMe Therapeutics presented new data showing that 23ME-01473 inhibits growth of non-small cell lung cancer in a patient-derived xenograft mouse model. The presentation also included data showing elevated plasma soluble and tumor expression levels of ULBP6 in squamous cell carcinomas and a subset of adenocarcinomas. These findings have led to the prioritization of four expansion cohort cancer types for potential further investigation during the Phase 2a dose expansion portion of the Phase 1/2a trial, which began in March 2024: head and neck squamous cell carcinoma, squamous non-small cell lung cancer, colorectal cancer and triple-negative breast cancer. The design of this Phase 1/2a trial was presented in a second Trials-In-Progress presentation at the ESMO Congress.

09:01 EDT Natera announces new data from GALAXY arm of ongoing CIRCULATE-Japan trial - Natera announced that new data from the GALAXY arm of the ongoing CIRCULATE-Japan trial was released today at the 2024 Congress of the European Society for Medical Oncology in Barcelona, Spain. GALAXY is one of the largest and most comprehensive prospective studies of circulating tumor DNA testing in resectable colorectal cancer. This latest analysis, which will also be published in Nature Medicine on September 16, provides the first evidence of the ability of Signatera-based molecular residual disease detection to predict overall survival. The data also demonstrates Signatera's ability to predict adjuvant chemotherapy benefit in resectable CRC, with ctDNA clearance as an indicator of a superior survival benefit compared to no clearance. In the study, 2,240 patients with stage II-IV CRC were monitored using Signatera after curative-intent surgery with a median follow-up of 23 months. Key takeaways include: Signatera status was predictive of overall survival. Signatera-positivity in the post-op MRD window was found to be significantly associated with worse OS compared to Signatera-negative patients with a 36-month OS of 71.80% vs. 96.0%, respectively. This 10x advantage in overall survival compares favorably to all known guideline-recommended biomarkers that have HRs for overall survival in a range of 1-4. Signatera status was predictive of an overall survival benefit from adjuvant chemotherapy. High-risk stage II and stage III-IV patients who were Signatera-positive after surgery and received ACT demonstrated superior OS, corresponding to a 50% reduction in the risk of death when treated with ACT. By comparison, the MOSAIC trial1, which was the last practice-changing study in adjuvant CRC, demonstrated a 16% reduction in risk of death. Signatera-negative patients did not derive an OS benefit from ACT. Signatera status remained the most significant predictor of recurrence. Signatera-positivity after surgery was the single most significant prognostic factor associated with inferior DFS and OS in a multivariate analysis that included all clinicopathologic risk factors currently in use. This is also reflected by the 36-month DFS difference between Signatera-positive and Signatera-negative patients at 16.7% versus 83.5%, respectively. The association of Signatera-positivity with a significantly increased risk for recurrence was observed across all pathologic stages. Sustained Signatera clearance after ACT was associated with improved survival. Patients who clear ctDNA and remained Signatera-negative had superior survival benefit with 24-month OS of 100%. This compares to patients who cleared ctDNA for a period of time but later become Signatera-positive, with 24-month OS of 82%, and patients who did not achieve ctDNA clearance, with 24-month OS of 61%. This finding further supports the utility of sustained ctDNA clearance as a surrogate endpoint for long-term outcomes.

08:55 EDT Incyte announces new early clinical data for INCB123667 - Incyte announced new early clinical data for INCB123667, a highly selective, potential first-in-class CDK2 inhibitor, in patients with advanced solid tumors. The trial results, presented during a mini-oral presentation at the European Society of Medical Oncology with new, updated data shared during the company's investor event, highlight the potential of INCB123667 as a differentiated treatment option for cancers with increased Cyclin E1 activity, amplification and/or overexpression in cells predictive of CDK2 dependency. In the trial, patients with advanced or metastatic solid tumors - including ovarian cancer, endometrial cancer, gastrointestinal cancer, HR+/HER2- breast cancer and triple negative breast cancer, among others - received varying doses of INCB123667 ranging from 50mg to 150mg using once-daily and twice-daily dosing schedules. New data from the Phase 1b dose expansion portion of the trial presented during Incyte's investor event, demonstrate single-agent antitumor activity, and decreases in circulating tumor DNA across a range of doses and regimens, notably in patients with ovarian cancer and endometrial cancer whose tumors overexpress Cyclin E1. The trial is ongoing, and the data will continue to mature. Of the 37 evaluable participants with platinum-resistant ovarian cancer treated at three selected dose levels in the expansion portion of the trial, nine participants experienced an overall response. The highest OR rate of 31.3% was found in the 50mg BID cohort. Additionally, a disease control rate of 75.7% was achieved in patients with ovarian cancer. In addition, 4 PRs were reported among patients with endometrial cancer. The Part 1b data build on results from the dose escalation portion of the trial evaluating the safety and tolerability of INCB123667 presented during a mini-oral presentation at ESMO. Results from the Part 1a dose escalation portion of the trial (data cut-off July 15, 2024) include: INCB123667 demonstrated a manageable safety profile. The most common hematologic treatment-related adverse events were thrombocytopenia, anemia and neutropenia. Strong selective inhibition of CDK2 was observed resulting in circulating tumor DNA reduction at all dose levels. During dose escalation, 39 out of 48 patients who had ctDNA measurements at cycle 1, day 1 and cycle 2, day 1 showed reductions in ctDNA. The study is ongoing. Plans are underway to initiate a pivotal study in ovarian cancer next year and evaluate INCB123667 in combination with other treatments.

08:41 EDT Merck announces OS results from pivotal Phase 3 KEYNOTE-A18 trial - Merck announced the first presentation of overall survival results from the pivotal Phase 3 KEYNOTE-A18 trial, also known as ENGOT-cx11/GOG-3047, investigating KEYTRUDA, Merck's anti-PD-1 therapy, in combination with concurrent chemoradiotherapy for newly diagnosed patients with high-risk locally advanced cervical cancer. At a median follow-up of 29.9 months, KEYTRUDA in combination with concurrent CRT reduced the risk of death by 33% versus concurrent CRT alone for these patients. For patients who received the KEYTRUDA-based regimen, the 36-month OS rate was 82.6% versus 74.8% for those who received concurrent CRT alone. Median OS was not reached in either group. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. KEYNOTE-A18 is one of four Phase 3 studies of a KEYTRUDA-based regimen in an earlier stage of cancer to demonstrate an OS benefit, in addition to KEYNOTE-522 in newly diagnosed, high-risk early-stage triple-negative breast cancer and KEYNOTE-671 in resectable stage II, IIIA or IIIB non-small cell lung cancer, as well as KEYNOTE-564 in renal cell carcinoma for patients at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. These results are being discussed with regulatory authorities worldwide. As previously reported, KEYNOTE-A18 met its other primary endpoint of progression-free survival in 2023. These PFS data were presented at the ESMO Congress 2023 and supported the U.S. Food and Drug Administration's approval of KEYTRUDA in combination with CRT for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer in January 2024. In the U.S., KEYTRUDA has two additional approved indications in cervical cancer: in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 [Combined Positive Score greater than or equal to1] as determined by an FDA-approved test; and as a single agent, for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 as determined by an FDA-approved test. As announced, data spanning more than 20 types of cancer are being presented from Merck's broad oncology portfolio and investigational pipeline at the ESMO Congress 2024. KEYNOTE-A18, also known as ENGOT-cx11/GOG-3047, is a randomized, double-blind Phase 3 trial sponsored by Merck and conducted in collaboration with the European Network for Gynaecological Oncology Trial groups and the GOG Foundation investigating KEYTRUDA in combination with CRT compared to placebo plus concurrent CRT for the treatment of newly diagnosed high-risk locally advanced cervical cancer where patients are treated with definitive intent. The primary endpoints are PFS and OS, and secondary endpoints include complete response rate, objective response rate and safety. The trial enrolled 1,060 patients who were randomized 1:1 to receive: KEYTRUDA every three weeks for five cycles concurrent with cisplatin weekly for five cycles radiotherapy, followed by KEYTRUDA every six weeks for 15 cycles; Placebo IV Q3W for five cycles concurrent with cisplatin weekly for five cycles and radiotherapy, followed by placebo IV Q6W for 15 cycles. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Grade greater than or equal to 3 treatment-related adverse eventsoccurred in 69.1% of patients receiving KEYTRUDA plus concurrent CRT versus 61.3% of patients receiving placebo plus concurrent CRT. No new safety concerns were identified. Immune-mediated adverse events of any grade occurred in 39% of patients receiving the KEYTRUDA regimen and 17% of patients receiving the placebo regimen. Grade 3-5 immune-mediated AEs occurred in 4.7% versus 1.3%, respectively. The most common of these all-grade immune-mediated AEs was hypothyroidism in patients receiving the KEYTRUDA regimen. Immune-mediated AEs led to one death among patients receiving the KEYTRUDA regimen.

08:07 EDT Johnson & Johnson announces new data from Phase 1b/2 OrigAMI-1 study - Johnson & Johnson announced new data from the Phase 1b/2 OrigAMI-1 study, which showed RYBREVANT combined with chemotherapy demonstrated promising rapid and durable antitumor activity in patients with RAS/BRAF wild-type metastatic colorectal cancer who have not previously received anti-epidermal growth factor receptor therapy. These data were presented in a mini-oral presentation at the European Society of Medical Oncology 2024 Congress. In the study, patients receiving RYBREVANT plus chemotherapy were either in their first or second line of treatment for mCRC and had not been treated with specific anti-EGFR therapies. Patients receiving FOLFOX were oxaliplatin-naive and patients receiving FOLFIRI were irinotecan-naive. Response was assessed by the investigator per RECIST v1.1. Forty-three patients were treated with RYBREVANT along with either FOLFOX or FOLFIRI. The median follow-up period was 7.3 months for RYBREVANT plus FOLFOX and RYBREVANT plus FOLFIRI. Patients treated with RYBREVANT plus chemotherapy achieved an overall response rate of 49 percent, median duration of response of 7.4 months and median progression-free survival of 7.5 months. Disease control was observed in 88 percent of patients. Clinically meaningful intrahepatic antitumor activity was observed among patients with liver metastases treated with RYBREVANT plus chemotherapy, demonstrating a significant reduction in liver tumors. Notably, nine patients were able to proceed to curative-intent surgery due to strong antitumor activity. The safety profile of RYBREVANT plus FOLFOX/FOLFIRI was manageable and consistent with each of the individual components, without any additive toxicity. No new safety signals were observed. The most frequent treatment-emergent adverse events were neutropenia, rash, stomatitis, infusion-related reactions and diarrhea. All IRRs were Grade 1 or 2 and there were no Grade 3 or higher IRR events reported. Treatment-related discontinuations of RYBREVANT were 10% for RYBREVANT plus FOLFOX and nine percent for RYBREVANT plus FOLFIRI. Pivotal Phase 3 registration trials evaluating RYBREVANT-based regimens as first- and second-line treatment in colorectal cancer are planned.

08:00 EDT Nuvalent highlights presentation of data from parallel lead programs - Nuvalent highlighted the presentation of updated data from the fully enrolled Phase 1 dose-escalation portions of the ongoing ARROS-1 Phase 1/2 clinical trial of zidesamtinib, a novel ROS1-selective inhibitor, and ALKOVE-1 Phase 1/2 clinical trial of NVL-655, a novel ALK-selective inhibitor, during two oral presentations at the European Society for Medical Oncology Congress 2024 in Barcelona, Spain. In addition, the company announced progress and provided updates on the development strategy and timelines for its parallel-lead programs zidesamtinib and NVL-655, including its development strategy for tyrosine kinase inhibitor-naive ALK-positive non-small cell lung cancer: Phase 2 portion of the ARROS-1 trial of zidesamtinib for TKI-naive and TKI pre-treated patients with advanced ROS1-positive NSCLC and other solid tumors: Between September 2023 and September 1, 2024, 227 patients were enrolled in the ongoing single-arm, multi-cohort Phase 2 portion of the ARROS-1 trial, which is designed with registrational intent. The company expects to report pivotal data from this trial in 2025. Phase 2 portion of the ALKOVE-1 trial of NVL-655 for TKI-naive and TKI pre-treated patients with advanced ALK-positive NSCLC and other solid tumors: Between February 2024 and September 1, 2024, 229 patients were enrolled in the ongoing single-arm, multi-cohort Phase 2 portion of the ALKOVE-1 trial, which is designed with registrational intent for TKI pre-treated patients. The company also expects to report pivotal data from this trial in 2025. ALKAZAR Phase 3 randomized, controlled trial of NVL-655 for TKI-naive patients with advanced ALK-positive NSCLC: The Phase 3 ALKAZAR trial will be a global, randomized, controlled trial designed to evaluate NVL-655 versus the current standard of care for the treatment of patients with TKI-naive ALK-positive NSCLC. Patients will be randomized 1:1 to receive NVL-655 monotherapy or ALECENSA monotherapy, reflecting input from collaborating physician-scientists and alignment with the U.S. Food and Drug Administration. The company plans to initiate the ALKAZAR study in the first half of 2025. The ALKAZAR trial is designed to enroll approximately 450 patients with TKI-naive ALK-positive NSCLC. The primary endpoint is progression free survival based on Blinded Independent Central Review. Secondary endpoints include PFS based on investigator's assessment, and BICR assessment of objective response rate, intracranial objective response rate, overall survival, and safety. From January 2022 to August 2023, the Phase 1 portion of ARROS-1 enrolled 104 patients. Patients received zidesamtinib orally at dose levels ranging from 25 to 150 mg once daily, and 100 mg QD was selected as the recommended Phase 2 dose. No clinically significant exposure-response relationships for safety and efficacy were observed and data are reported across all doses. The patient population was heavily pre-treated, with a median of 3 prior lines of therapy. 69% of patients had greater than or equal to 2 prior ROS1 TKIs, and 66% had prior chemotherapy. Notably, 55% of patients received prior lorlatinib and 21% received prior repotrectinib, highlighting the differentiated nature of this population from prior trials of other ROS1 inhibitors. 52% had history of CNS metastases, including cases of disease progression following treatment with the brain-penetrant TKIs lorlatinib and/or repotrectinib. As of the cut-off date of July 1, 2024, 71 pre-treated patients with ROS1-positive NSCLC were response-evaluable. The median follow-up for the all-treated population was 12.1 months. In the subset of patients with confirmed ROS1 G2032R resistance mutation, the ORR was 72% for repotrectinib-naive patients. IC-ORR was 50% in intracranial response-evaluable patients with measurable CNS lesions, of which 7/8 patients had been previously treated with the brain-penetrant TKIs lorlatinib and/or repotrectinib. The mIC-DOR was not reached, with no CNS progression observed among confirmed CNS responders. Zidesamtinib was well-tolerated with a preliminary safety profile that was favorable and consistent with its ROS1-selective, TRK sparing design. Among these most frequent TRAEs, there was a single grade 3 event of weight increase. No discontinuation due to TRAEs occurred. Dose reductions due to TRAEs occurred in 8% of patients. A maximum tolerated dose was not identified. The company believes these preliminary data demonstrate the potential for zidesamtinib to address a medical need for the third-line treatment of ROS1-positive NSCLC where no approved therapies have demonstrated clinical benefit, and to provide a differentiated option in the second line where there also remains a medical need. Additionally, the company believes that these data in heavily pre-treated patients could have the potential to translate to deep, durable responses in the front-line setting. Further investigation of zidesamtinib for both TKI-naive and TKI pretreated patients with ROS1-positive NSCLC is underway in the Phase 2 portion of the ARROS-1 clinical trial, designed with registrational intent. The company expects to report pivotal data in 2025. From June 2022 to February 2024, the Phase 1 portion of ALKOVE-1 enrolled 133 patients. Patients received NVL-655 orally at dose levels ranging from 15 to 200 mg QD, and 150 mg QD was selected as the RP2D. The patient population was heavily pre-treated, with a median of 3 prior lines of therapy. 46% of patients had greater than or equal to 3 prior ALK TKIs, and 56% had prior chemotherapy. Notably, 84% of patients received prior lorlatinib and 51% had any secondary ALK resistance mutation including 26% with compound ALK mutations, highlighting the differentiated nature of this population from prior trials of investigational ALK inhibitors. 56% had history of CNS metastases, including cases of disease progression following treatment with the brain-penetrant TKI lorlatinib. As of the cut-off date of June 15, 2024, 103 heavily pre-treated patients with ALK-positive NSCLC treated across all doses were response-evaluable, of whom 39 were treated at the RP2D. The median follow-up for the all-treated population was 8.0 months.

07:50 EDT Pfizer announces follow-up results from Phase 2 single-arm PHAROS trial - Pfizer announced longer-term follow-up results from the Phase 2 single-arm PHAROS clinical trial evaluating the efficacy and safety of BRAFTOVI in combination with MEKTOVI for patients with BRAF V600E-mutant metastatic non-small cell lung cancer (NSCLC). After an additional 18 months of follow-up, the objective response rate and the median duration of response as assessed by independent radiology review were 75% and 40 months in treatment-naive patients and 46% and 16.7 months in previously treated patients, respectively. In addition, after approximately three years of follow-up in treatment-naive patients, the median progression-free survival with BRAFTOVI + MEKTOVI was 30.2 months, while median overall survival was not yet reached. These data will be presented today during a late-breaking oral session at the European Society for Medical Oncology Congress 2024 in Barcelona, Spain. Lung cancer is the number one cause of cancer-related death around the world.1 NSCLC accounts for approximately 80-85% of lung cancers, with BRAF V600E mutations occurring in about 2% of patients with NSCLC. Understanding the role of the mitogen-activated protein within the pathway including BRAF V600E-mutant metastatic NSCLC. The Phase 2 PHAROS trial is an open-label, multicenter, single arm study examining BRAFTOVI + MEKTOVI combination therapy in treatment-naive and previously treated patients with BRAF V600E-mutant metastatic NSCLC. Notably, upon longer-term follow-up in previously treated patients, BRAFTOVI + MEKTOVI showed a median PFS of 9.3 months and a median OS of 22.7 months, with a safety profile that was consistent with previous findings; no new safety concerns were identified. In this analysis, treatment-related adverse events led to dose reduction in 26% of patients, and to permanent discontinuation in 16% of patients. Nausea, diarrhea, and fatigue remained the most common treatment-related AEs. In addition to PHAROS, safety lead-in data from the ongoing Phase 3 BREAKWATER study investigating BRAFTOVI in combination with cetuximab and FOLFIRI chemotherapy in previously untreated BRAF V600E-mutant metastatic colorectal cancer (CRC) will also be presented as a mini-oral session at ESMO.

07:37 EDT J&J announces updated results from Phase 3 MARIPOSA-2 study - Johnson & Johnson announced updated results from the Phase 3 MARIPOSA-2 study which showed RYBREVAN combined with chemotherapy led to consistent benefit across post-progression outcomes in adult patients with previously treated non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or L858R substitution mutations. The data also reveal a favorable trend toward improved overall survival compared to chemotherapy alone. Results were presented at the European Society of Medical Oncology 2024 Congress. At the second interim analysis, with a median follow-up of 18.1 months, 50 percent of patients treated with RYBREVANT plus chemotherapy were still alive at the 18-month landmark, compared to 40 percent of those receiving chemotherapy alone. RYBREVANT plus chemotherapy showed a significant improvement in treatment discontinuation rates, with nearly five times as many patients remaining on therapy at 18 months compared to chemotherapy. Additionally, patients treated with RYBREVANT plus chemotherapy experienced a 27 percent reduction in the risk of symptomatic progression. The time to subsequent therapy was significantly prolonged with the RYBREVANT combination compared to chemotherapy, which also reduced the risk of second disease progression or death by 36 percent. In the MARIPOSA-2 study, the safety profile of RYBREVANT in combination with chemotherapy was consistent with the established profiles of the individual treatments. Permanent discontinuation of RYBREVANT due to adverse reactions occurred in 11 percent of patients. RYBREVANT(R) plus chemotherapy received approval by the European Commision in August 2024 as a treatment for patients with previously treated NSCLC with common EGFR mutations based on the superior efficacy and safety profile demonstrated in this study.

07:10 EDT Nuvation announces pooled data from pivotal Phase 2 TRUST-I, TRUST-II studies - Nuvation Bio announced pooled data from the pivotal Phase 2 TRUST-I and TRUST-II studies evaluating taletrectinib, an investigational next-generation ROS1 TKI. The findings will be highlighted in a poster presentation on September 14, 2024, at the European Society of Medical Oncology Congress 2024 in Barcelona, Spain. The pooled efficacy and safety data from the TRUST-I and TRUST-II studies presented at ESMO are as of June 7, 2024; both studies remain ongoing. The ESMO data set includes 337 patients with advanced ROS1+ NSCLC who received 600mg of taletrectinib orally once daily in 21-day cycles. The primary endpoint of these registrational studies is confirmed objective response rate as assessed by an independent review committee. Key secondary endpoints include intracranial cORR, DOR, PFS, and safety. The pooled efficacy analyses included 160 patients with advanced ROS1+ NSCLC who had not previously been treated with a ROS1 TKI and 113 patients who had previously been treated with crizotinib or entrectinib. Among these two populations, 94% of patients had stage IV NSCLC. In addition, 20% of TKI-naive and 37% of TKI-pretreated patients received prior chemotherapy, while 23% of TKI-naive and 49% of TKI-pretreated patients had brain metastases at baseline. The efficacy results, independently assessed by an IRC, showed in TKI-naive patients: Tumors shrank in 89% of taletrectinib-treated patients. Measurable brain metastases shrank in 77%of taletrectinib-treated patients. After median follow-up of 21 months, the median DOR and the median PFS were 44 months and 46 months, respectively. In TKI-pretreated patients, it showed that: Tumors shrank in 56% of taletrectinib-treated patients. Measurable brain metastases shrank in 66% of taletrectinib-treated patients. Tumors shrank in 62% of taletrectinib-treated patients with G2032R mutations. After median follow-up of 21 months, the median DOR and the median PFS were 17 months and 10 months, respectively. The pooled safety analysis included 337 patients with advanced ROS1+ NSCLC. The results demonstrated a favorable safety and tolerability profile, with a low incidence and a limited spectrum of neurologic TEAEs and a low rate of treatment discontinuation. The incidence of neurologic TEAEs was low. The rate of treatment discontinuation due to TEAEs was 7% and the rate of dose reduction due to TEAEs was 29%.

07:05 EDT Sutro announces data from Phase 1b study of Luvelta in combo with Bevacizumab - Sutro Biopharma announced updated data from the ongoing Phase 1b study of luveltamab tazevibulin in combination with bevacizumab for patients with epithelial ovarian cancer in a poster presentation at the 2024 European Society For Medical Oncology Congress in Barcelona, Spain. In this study, luvelta plus bevacizumab has demonstrated encouraging antitumor activity in patients with late-stage ovarian cancer irrespective of Folate Receptor-alpha expression, including patients with no FRalpha expression, and prior bevacizumab treatment, with an overall response rate of 35%. These early data in combination may offer a non-biomarker driven approach to treat patients with EOC. The expansion phase of the study is ongoing at the recommended phase 2 dose of luvelta in combination with bevacizumab with an additional 23 patients enrolled to date; initial data is expected in the first half of 2025. 18 patients were enrolled; one patient remains on treatment. Luvelta plus bevacizumab demonstrated encouraging antitumor activity in 17 RECIST evaluable patients: At the RP2D, an Objective Response Rate of 56% was observed; no patients had a response at 3.5 mg/kg and 50% of patients had a response at 5.2 mg/kg. An ORR of 35% was observed in the overall population with a median duration of response of 9.3 months. In patients with greater than or equal to 25% FRalpha expression, an ORR of 44% was observed; in patients with less than25% FRalpha expression, an ORR of 29% was observed. No new safety signals were observed compared with either agent alone; consistent with previous reported luvelta safety results, the most common adverse event was neutropenia.

06:55 EDT Bicycle Therapeutics presents updated results across oncology pipeline at ESMO - Bicycle Therapeutics announced updated Phase 1/2 clinical results for Bicycle Toxin Conjugate zelenectide pevedotin in metastatic urothelial cancer; BTC molecule BT5528 in advanced solid tumors, such as mUC and ovarian; and Bicycle Tumor-Targeted Immune Cell Agonist BT7480 in advanced solid tumors. The company also shared an analysis of peripheral neuropathy, a key adverse event of interest associated with monomethyl auristatin E-based drug conjugates, in patients treated with BTC molecules. These data will be presented during a poster session at the European Society for Medical Oncology Congress 2024 in Barcelona today. Zelenectide pevedotin is a BTC molecule targeting Nectin-4, a well-validated tumor antigen, designed to overcome the significant toxicity associated with other drug conjugate approaches. Updated results from the ongoing Phase 1/2 Duravelo-1 trial evaluating 5 mg/m2 weekly of zelenectide pevedotin monotherapy in 45 mUC patients who had not previously been treated with enfortumab vedotin showed: Among 38 efficacy-evaluable patients, a 45% overall response rate, including 1 confirmed complete response and 16 partial responses. Stable disease was maintained in 9 patients, and 12 patients experienced progressive disease. A median duration of response of 11.1 months among the 14 patients with confirmed responses. An emerging differentiated safety profile, particularly around adverse events of interest such as peripheral neuropathy, skin reactions and eye disorders. Notably, there were no Grade greater than or equal to 3 treatment-related adverse events of peripheral neuropathy, skin reactions or eye disorders, and patients with pre-existing peripheral neuropathy were unlikely to develop worsening peripheral neuropathy during treatment with zelenectide pevedotin. The global Phase 2/3 Duravelo-2 registrational trial of zelenectide pevedotin in patients with mUC is currently enrolling. Additional data updates for zelenectide pevedotin in combination with pembrolizumab in first line mUC and monotherapy in late line triple-negative breast cancer and non-small cell lung cancer are planned for later this year. BT5528 is a BTC molecule targeting EphA2, a tumor antigen that is widely expressed in many cancers and has historically been difficult to target using other drug conjugate approaches. Updated results from the ongoing Phase 1/2 trial evaluating 6.5 mg/m2 every two weeks and 5 mg/m2 weekly of BT5528 monotherapy in patients with advanced solid tumors showed: Among 113 efficacy-evaluable patients, a 12% ORR in patients with advanced solid tumors. The highest anti-tumor activity in mUC, with a 34% ORR in all efficacy-evaluable patients enrolled in the dose escalation and expansion cohorts. Among patients receiving 6.5 mg/m2 every two weeks, a 31% ORR was observed in the dose escalation and expansion cohort and a 45% ORR was observed in the expansion cohort only. A lower but acceptable ORR of 27% was observed in patients receiving 5 mg/m2 weekly. No objective responses in patients with ovarian cancer who received 5 mg/m2 weekly. However, 5 patients maintained stable disease. A suggested correlation between EphA2 expression and response. Among 14 patients with mUC who had available immunohistochemistry and response data, a 43% ORR was observed in EphA2-positive patients compared to a 20% ORR in EphA2-negative patients. A clearly differentiated emerging safety profile, with none of the hemorrhage events or hematological toxicities that have been associated with other EphA2-targeting drug conjugates. The company has begun assessing BT5528 at 6.5 mg/m2 every two weeks in combination with nivolumab. Results from this cohort are expected in 2025. Low rates of treatment-related peripheral neuropathy following monotherapy treatment with BTC molecules zelenectide pevedotin or BT5528. In 149 patients treated with zelenectide pevedotin and 74 patients treated with BT5528 from ongoing Phase 1/2 studies, results showed: TRPN in 28% of patients treated with zelenectide pevedotin and 19% of patients treated with BT5528, nearly all of which were low grade. One Grade 3 event was reported in a patient treated with zelenectide pevedotin following prior therapy with enfortumab vedotin. No Grade 3-4 events were observed for BT5528. Among zelenectide pevedotin-treated patients with peripheral neuropathy at baseline, 80% did not develop TRPN during treatment. TRPN resulted in few dose modifications across the overall patient populations for zelenectide pevedotin and BT5528, and no drug withdrawals were necessary for either BTC molecule. TRPN had completely resolved in 14% and 21% of patients, and 26% and 21%, respectively, had some resolution or improvement at time of reporting, though post-treatment follow-up was limited. Median time to resolution or improvement of TRPN was 2.2 weeks for zelenectide pevedotin and 1.7 weeks for BT5528. The data support the hypothesis that the antibody-drug construct may be a primary driver of peripheral neuropathy rather than MMAE toxicity as was previously believed. BT7480 is a Nectin-4 targeted CD137 agonist designed to overcome immune agonist toxicities and activate the immune system in Nectin-4 expressing tumors. Initial data from the Phase 1/2 dose escalation trial evaluating BT7480 in patients with advanced solid tumors showed: Among 39 patients assigned to receive one of 10 different doses of BT7480, an emerging differentiated safety and tolerability profile with a low number of severe adverse events. Low rates of Grade greater than or equal to3 TRAEs and of treatment-related severe adverse events were reported, with no such events among those receiving the highest dose of 3.5 mg/kg. Best overall response of stable disease in 13 patients, 5 of whom had NSCLC. Stable disease was prolonged in 3 patients, 2 with NSCLC and 1 with anal cancer. There were 2 unconfirmed partial responses, both in patients with cervical cancer. Preliminary biomarker analyses that support BT7480 dual targeting of CD137 and Nectin-4 as demonstrated by enhanced immune cell activation, aligned with the proposed mechanism of action of BT7480. As the maximum tolerated dose for BT7480 has not yet been reached, the company is continuing dose exploration in combination studies, starting with nivolumab.

06:50 EDT IO Biotech announces results from Phase 2 trial of IO102-IO103 - IO Biotech (IOBT) announced promising data from the Phase 2 basket trial of IO102-IO103, the company's lead investigational therapeutic cancer vaccine candidate, in combination with Merck's (MRK) anti-PD-1 therapy KEYTRUDA at the 2024 ESMO Congress in Barcelona from September 13-17. The presentation contained clinical and biomarker data from a cohort of patients with recurrent or metastatic squamous cell carcinoma of the head and neck with PD-L1 CPS greater than or equal to 20, contributing to the growing body of research supporting the potential clinical benefit of this combination regimen for these patients. The data from 18 efficacy evaluable patients demonstrated: Achievement of the primary endpoint - confirmed 44.4% overall response rate in a PD-L1 high population of patients with SCCHN irrespective of HPV status. An encouraging 6.6-month median progression-free survival. A 66.7% disease control rate. A safety profile consistent with previously reported data when combined with anti-PD-1 monotherapy. T-cell responses to both IO102 and IO103 were detected after treatment.