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18:11 EDT Amgen announces detailed results from global Phase 3 CodeBreaK 200 trial - Amgen announced detailed results from the global Phase 3 CodeBreaK 200 trial, which showed once-daily oral LUMAKRAS/LUMYKRAS led to significantly superior progression-free survival and a significantly higher objective response rate in patients with KRAS G12C-mutated non small cell lung cancer, compared with intravenous chemotherapy, docetaxel. LUMAKRAS significantly improved PFS as determined by Blinded Independent Central Review compared to docetaxel in heavily pre-treated patients, and PFS favored LUMAKRAS across all clinically relevant subgroups. The proportion of patients with PFS at one year was 25% for LUMAKRAS versus 10% for docetaxel. LUMAKRAS demonstrated a significantly higher ORR than docetaxel with double the response rates in the LUMAKRAS arm and showed consistent benefit across other efficacy secondary endpoints, including improved disease control rate. Overall survival was not significantly different between treatment arms. The study was not powered to detect a statistical difference in OS, and cross-over from docetaxel to LUMAKRAS was permitted after disease progression. There were fewer treatment-related adverse events for LUMAKRAS versus docetaxel. Grade greater than or equal to 3 TRAEs and serious TRAEs were lower with LUMAKRAS compared to docetaxel. Data from CodeBreaK 200 will be submitted to global regulatory authorities where LUMAKRAS/LUMYKRAS has accelerated approval or conditional marketing authorization. LUMAKRAS is the only KRASG12C inhibitor approved anywhere in the world with approval in 44 markets, including the United States, the European Union, the United Kingdrom and Japan. CodeBreaK 200 is the first randomized, controlled clinical trial for a KRASG12C inhibitor.

17:11 EDT Edgewise announces 4-month results from ARCH open study of EDG-5506 - Edgewise Therapeutics positive 4-month interim results from the ongoing ARCH study, an open label, single-center study assessing the safety, tolerability, impact on muscle damage biomarkers, and pharmacokinetics of EDG-5506 in adults with BMD. EDG-5506 is an investigational orally administered small molecule myosin modulator designed to protect injury-susceptible fast skeletal muscle fibers in dystrophinopathies such as Duchenne muscular dystrophy and BMD. The twelve adults with BMD enrolled in the ARCH study were dose escalated to daily 15 mg oral doses of EDG-5506 at night after having initially received a 10 mg dose during the first 2 months of the study. Plasma PK at 4 months reached the target exposures observed in the Phase 1b study where BMD participants were dosed with 20 mg EDG-5506 once-daily for two weeks. EDG-5506 was well-tolerated in all participants with no discontinuations or dose reductions. The most common adverse events observed to date were dizziness, drowsiness, and headache. All eligible patients have subsequently been dose escalated to 20 mg daily as per protocol. Treatment with EDG-5506 led to a significant decrease in key biomarkers of muscle damage when assessed by laboratory assays. Importantly, CK and fast skeletal muscle troponin I were reduced by an average of 29% and 74%, respectively, after 4 months. While CK reductions were sustained and in line with observations made at 2 months, mean fast skeletal muscle troponin I levels decreased with continued exposure to EDG-5506. Similar to observations made after 2 months, both CK and fast skeletal muscle troponin I were significantly decreased in the context of typical everyday activity levels as measured with a pedometer. After 4 months of EDG-5506 dosing, NSAA increased by an average of 1.17 points compared to pre-therapy baseline. Remarkably, nine of the twelve participants showed either a functional improvement or exhibited no decline on NSAA relative to their baselines. The NSAA improvements observed after only 4 months of EDG-5506 dosing differ from trajectories observed in the natural history study reported by Bello et al. (2016)1, one of the most comprehensively characterized BMD cohorts, in which the yearly decline was 1.22 NSAA points. These observations were further corroborated by an independent study from van de Velde et al. (2021)2, which showed a decline of 2.5 NSAA points over 2 years. The company believes the 4-month ARCH study data with EDG-5506 provide further support that reducing contraction-induced damage in dystrophic muscle has the potential to preserve and improve muscle function while preventing disease progression in dystrophinopathies.

15:56 EDT Grail announces final results from PATHFINDER study at ESMO - Grail announced final results from the interventional PATHFINDER study, which evaluated multi-cancer early detection screening using a blood test and the clinical care pathways following a "cancer signal detected" MCED test result in 6,662 individuals aged 50 years or older, an age group at elevated risk for cancer. PATHFINDER was a single-arm study that measured the time required to achieve diagnostic resolution following a "cancer signal detected" MCED blood test result and the number and types of diagnostic tests that were used. MCED test performance was a key secondary endpoint, including positive predictive value and the accuracy of the predicted cancer signal origin. Participants were followed for 12 months after enrollment. If a participant had a negative MCED test at enrollment but developed a cancer within the 12-month follow-up, it was counted as an MCED false negative. Test performance was measured using both an earlier version of Galleri and a refined version of Galleri. The earlier version of the test was refined to reduce the detection of pre-malignant hematologic conditions, which are fairly common, and improve prediction of the cancer signal origin. The study was completed with the earlier version of the test and then the blood samples were retested in a pre-specified retrospective analysis using the refined Galleri test. A cancer signal was detected in 92 participants, two of whom began workup prior to the return of their MCED test results. Of these, 35 participants were diagnosed with 36 cancers. Among the confirmed cancers, 71% of participants had cancer types that have no routine cancer screening available. Nearly half of the non-recurrent cancers were found in early-stages. Standard of care screening identified 29 cancers, and another 56 cancers were diagnosed because symptoms appeared or tumors were found incidentally or from monitoring for cancer recurrence. The cancer signal origin prediction had a 97% accuracy and directed physician clinical workup, leading to resolution of the cancer diagnosis in less than three months for most participants with a true positive signal, and in less than two months for half of them. The median time to diagnostic resolution was longer for false positive results; 44% of these participants had scheduled follow-up imaging or procedures three or more months later, contributing to the longer time to resolution. Most participants underwent imaging procedures, such as scans or MRIs, following true and false-positive results. As expected, most true positive participants underwent an invasive procedure to confirm a cancer diagnosis. Three underwent endoscopies triggered by the predicted cancer signal origin, and 24 had procedures triggered only by abnormal imaging, physical, or laboratory findings, including three surgical biopsies. A smaller proportion of false positive participants had invasive procedures. Five had procedures triggered by CSO predictions, and 12 had procedures triggered only by abnormal imaging, physical, or laboratory findings, or by their medical history. No study-related serious adverse events were reported as a result of MCED testing in the study, and there were no adverse events reported from diagnostic workups. The PPV was 43.1% with the refined test and 38.0% with the earlier version. Specificity, or the percentage of true negatives, of the refined test was 99.5%, and 99.1% with the earlier version, and the false positive rate for both versions was less than 1%. Test performance was consistent with the interim analysis and the previous case-controlled Circulating Cell-free Genome Atlas study. An analysis of participant-reported outcomes of anxiety, distress, and satisfaction related to MCED testing from the study were also presented at the ESMO Congress 2022. PATHFINDER participants completed patient-reported outcomes assessments before MCED testing, after receiving MCED test results, and at the end of the study. The analysis found 97.1% of participants reported a high level of satisfaction with the test, including those who had both true positive and false-positive results. As expected, a higher level of anxiety was seen in participants following a positive result, but that resolved to pre-MCED test levels within 12 months. GRAIL conducted an analysis of the first 38,154 Galleri commercial test results to monitor Galleri performance in a real world setting. The analysis showed a 1.1% cancer signal detection rate. As seen in clinical trials, the signal detection rate increases with age and male sex, consistent with the National Cancer Institute's Surveillance, Epidemiology, and End Results Program statistics. Among 326 patients with a positive cancer signal detected result and short-term follow up, 108 cancers have been confirmed by the ordering providers to-date, representing 28 different cancer types. Of the 108 patients with a provider-confirmed cancer diagnosis, 64 had no recommended cancer screening test. Provider-confirmed cancers include, among others, Stage I pancreatic, head and neck, endometrial, esophageal, and gastrointestinal stromal tumor cancers and Stage II rectal, liver, and head and neck cancers. GRAIL, is a subsidiary of Illumina currently held separate from Illumina under the terms of the Interim Measures Order of the European Commission dated 29 October 2021.

15:45 EDT Relay Therapeutics announces late breaking interim data for RLY-4008 - Relay Therapeutics announced late breaking interim clinical data in an oral presentation for RLY-4008, an investigational, potent, selective and oral small molecule inhibitor of fibroblast growth factor receptor 2, in a global phase 1/2 clinical trial in patients with FGFR2-altered CCA and multiple other solid tumors. The interim data presented at the European Society for Medical Oncology Congress demonstrate an 88% overall response rate at the pivotal dose of RLY-4008, 70 mg once daily, as of August 1, 2022, and further support our hypothesis that selective inhibition of FGFR2 can improve the treatment for patients with FGFR2-driven tumors. The data presented at the ESMO Congress were based on an August 1, 2022 data cut-off date from both the dose escalation and dose expansion phases of the trial. The interim data included a safety database of 195 patients, with 89 patients treated at the pivotal dose of 70 mg QD, of which 17 were FGFRi-naive FGFR2-fusion CCA patients eligible for efficacy evaluation. 15 out of 17 of the efficacy evaluable patients at the pivotal dose experienced a partial response resulting in an 88% interim ORR. 13 out of 15 responders remain on treatment; 1 responder came off study to be resected with curative intent. The two patients with best response of stable disease remain on treatment. More broadly across all dose levels and schedules, 38 FGFRi-naive FGFR2-fusion CCA patients were eligible for efficacy evaluation, of which 24 experienced a partial response resulting in a 63% interim ORR. The interim safety analysis as of the August 1, 2022 cut-off date was generally consistent with the analysis from the June 2022 data disclosure: Most treatment emergent adverse events were expected FGFR2 on-target, low-grade, monitorable, manageable and largely reversible. There were no observed Grade 4 or 5 adverse events. Off-target toxicities of hyperphosphatemia and diarrhea continued to be clinically insignificant. The pivotal cohort of FGFRi-naive FGFR2-fusion CCA patients is anticipated to be fully enrolled in the second half of 2023. Initial data from the non-CCA expansion cohorts are expected to be presented in 2023. The entirety of the dose escalation data is expected to be presented at a medical meeting or published by the end of the first half of 2023.

15:36 EDT AstraZeneca presents results from ADAURA Phase III trial - Updated results from the pivotal ADAURA Phase III trial showed that AstraZeneca's TAGRISSO demonstrated a sustained, clinically meaningful improvement in disease-free survival compared to placebo in the adjuvant treatment of patients with early-stage epidermal growth factor receptor-mutated non-small cell lung cancer after complete tumor resection with curative intent. With an additional two years of follow-up from the 2020 readout, allowing all patients the opportunity to complete three years of adjuvant treatment, TAGRISSO reduced the risk of disease recurrence or death by 77% in the primary analysis population and by 73% in the overall trial population. A median DFS of nearly five and a half years was seen in both the primary and overall populations treated with TAGRISSO, compared to 21.9 and 28.1 months in the primary and overall populations, respectively, treated with placebo. While up to 30% of all patients with NSCLC may be diagnosed early enough to have surgery with curative intent, recurrence is still common in early-stage disease. Historically, approximately half of patients diagnosed in Stages I-II, and three quarters of patients diagnosed in Stage III, have experienced recurrence within five years of resection. Results from an additional, prespecified exploratory analysis showed TAGRISSO reduced the risk of central nervous system disease recurrence by 76% in patients with Stage II-IIIA disease. At four years, 90% of patients in the TAGRISSO arm were disease-free in the brain and spinal cord compared to 75% of patients in the placebo arm. CNS disease recurrence refers to the spread of tumors to the brain or spinal cord, a frequent complication of EGFRm NSCLC associated with an especially poor prognosis.

15:21 EDT ImmunoGen presents additional analyses evaluating mirvetuximab soravtansine - ImmunoGen announced findings from an analysis of patient-reported outcomes with mirvetuximab soravtansine versus chemotherapy in the randomized Phase 3 FORWARD I study in platinum-resistant ovarian cancer. The company also announced population pharmacokinetic and exposure response analyses across multiple clinical trials evaluating mirvetuximab monotherapy in folate receptor alpha-positive ovarian cancer. The Phase 3 FORWARD I trial enrolled 366 patients who were randomized 2:1 to receive either mirvetuximab or the physician's choice of single-agent chemotherapy. Eligible patients were diagnosed with platinum-resistant ovarian cancer that expresses medium or high levels of FRalpha and were treated with up to three prior regimens. The primary endpoint was progression-free survival, which was assessed in the entire study population and in the subset of patients with high FRalpha expression. Patients completed PRO assessments during screening, on day 1 of cycle 1, every 9 weeks thereafter until disease progression, and at the end of treatment visit. In the intent-to-treat population, a statistically significant improvement in the number of patients achieving a 15-point improvement in gastrointestinal symptoms was observed at week 8/9 in patients treated with mirvetuximab versus chemotherapy. The likelihood of GI symptom deterioration was 70% lower with mirvetuximab in the ITT population compared with chemotherapy. In the FRalpha-high population, the likelihood of GI symptom deterioration was 80% lower with mirvetuximab compared with chemotherapy. In both the ITT and FRalpha-high patient populations, improvements were seen with mirvetuximab compared with chemotherapy across multiple side effects, including sexuality, hair loss, pain severity, body image, and general improvement in ovarian cancer-specific symptoms. In both the ITT and FRalpha-high patient populations, there were statistically significant benefits in physical functioning for mirvetuximab over chemotherapy. An ER analysis was conducted across three studies - the Phase 1 IMGN853-0401 trial, the Phase 3 FORWARD I trial, and the Phase 3 SORAYA trial - to understand the relationship between exposure to single-agent mirvetuximab and the efficacy and safety responses observed in patients with FRalpha-positive tumors. Both efficacy, in terms of objective response rate and PFS, and ocular adverse events were higher with increased exposure to mirvetuximab. These data highlight the importance of adherence to recommended mirvetuximab dosing guidelines in clinical practice. A PK analysis, taking into account patient demographics and clinical characteristics, was conducted across three studies - IMGN853-0401, FORWARD I, and SORAYA - to understand the efficacy and safety of mirvetuximab in patients with FRalpha-positive tumors. Dosing adjustments do not appear to be necessary for patients with mild or moderate renal impairment or mild hepatic impairment. The analyses support the final recommended dose of 6 mg/kg based on adjusted ideal body weight every 3 weeks with balanced efficacy and safety.

15:03 EDT Merck announces data from exploratory analyses of Phase 3 studies in NSCLC - Merck, known as MSD outside of the United States and Canada, today announced KEYTRUDA, Merck's anti-PD-1 therapy, plus chemotherapy continued to demonstrate a survival benefit and durable responses in two five-year exploratory analyses of pivotal Phase 3 studies as first-line treatment for metastatic non-small cell lung cancer. For patients with metastatic nonsquamous NSCLC, data from KEYNOTE-189 demonstrated KEYTRUDA plus pemetrexed and platinum chemotherapy had a five-year overall survival rate of 19.4% versus 11.3% for chemotherapy alone. The KEYTRUDA-pemetrexed-platinum chemotherapy combination reduced the risk of death by 40%. At five years, KEYTRUDA plus pemetrexed and cisplatin or carboplatin more than doubled the median OS compared to chemotherapy alone. For patients with metastatic squamous NSCLC, results from KEYNOTE-407 showed the five-year OS rate for KEYTRUDA plus carboplatin-paclitaxel or nab-paclitaxel was 18.4% versus 9.7% for chemotherapy alone. KEYTRUDA plus carboplatin-paclitaxel or nab-paclitaxel reduced the risk of death by 29% versus chemotherapy alone. The median OS was 17.2 months for the KEYTRUDA plus chemotherapy group versus 11.6 months for the chemotherapy group. KEYTRUDA is the first immunotherapy to demonstrate a sustained five-year survival benefit both in combination with chemotherapy and as monotherapy for the first-line treatment of NSCLC. In addition to NSCLC, five-year survival data for KEYTRUDA have been presented in three other types of cancer, including bladder cancer, head and neck cancer and melanoma. Results from KEYNOTE-189 and KEYNOTE-407 were presented during a mini oral session at the European Society for Medical Oncology Congress 2022. Five-year OS data from KEYNOTE-024, which evaluated KEYTRUDA monotherapy versus chemotherapy for the first-line treatment of patients with metastatic NSCLC whose tumors expressed PD-L1, were presented at ESMO 2020. Five-year OS data from KEYNOTE-042, which evaluated KEYTRUDA monotherapy versus platinum-based chemotherapy for the first-line treatment of patients with metastatic NSCLC whose tumors expressed PD-L1, were presented at SITC 2021.

14:49 EDT Veracyte announces new data from Phase 3 of STAMPEDE platform protocol - Veracyte announced that new data from a Phase 3 trial of the multi-center, multi-national, randomized STAMPEDE platform protocol confirm the ability of the company's Decipher Prostate Genomic Classifier to identify men with advanced prostate cancer who are more likely to benefit from intensified treatment with abiraterone acetate and prednisolone in addition to standard-of-care androgen-deprivation therapy. The findings were shared in an oral presentation today at the European Society for Medical Oncology Congress 2022 and support the company's continued expansion of its high-value genomic tests for patients in the United States and globally. The STAMPEDE - Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy - protocol involves more than 10,000 men to date with high-risk, non-metastatic or metastatic prostate cancer who are starting long-term androgen-deprivation therapy for the first time and are randomized to new treatments in seven Phase 3 trials. In this post-hoc analysis of the abiraterone acetate trial, Prof. Attard and colleagues evaluated the prognostic ability of the Decipher Prostate test among 781 men who were randomized to receive standard-of-care ADT with or without abiraterone acetate and prednisolone. They found that Decipher was prognostic in both the M0 and M1 patients, with higher Decipher scores associated with worse overall survival in M1 patients, and worse metastasis-free survival in M0 patients. Additionally, study findings suggest that men with high Decipher scores who received AAP had the greatest improvement in outcomes, while those with low Decipher scores received less absolute oncologic benefit from the addition of AAP. Among the other abstracts presented at the ESMO conference, researchers shared data derived from Veracyte's Decipher GRID, a database of more than 100,000 whole-transcriptome profiles from patients with urologic cancers. Decipher GRID has led to the discovery or development of more than 400 genomic signatures that can be leveraged to help advance understanding of prostate and other urologic cancers, as well as to support biopharmaceutical companies' targeted-therapy development programs. In a poster presentation, researchers shared data showing that the Decipher GRID androgen receptor activity signature is prognostic for outcomes in men with castration-sensitive prostate cancer that has spread to no more than three other sites in the body. The researchers concluded that the GRID AR-A signature is prognostic for outcomes in men with omCSPC treated with metastasis-directed therapy and that patients with a low AR-A score receive the most benefit from the addition of ADT to MDT.