AstraZeneca and Merck report prostate cancer data

AstraZeneca, Merck presents results from Phase 3 PROfound trial of LYNPARZA

AstraZeneca (AZN) and Merck (MRK) presented detailed results from the Phase 3 PROfound trial in 387 men with metastatic castration-resistant prostate cancer who have a mutation in their homologous recombination repair genes and whose disease had progressed on prior treatment with new hormonal agent treatments e.g. abiraterone or enzalutamide.

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AstraZeneca and Merck report prostate cancer, Stockwinners

The trial was designed to analyze men with mCRPC harboring HRR-mutated genes in two cohorts: the primary endpoint was in those with mutations in BRCA1/2 or ATM genes and then, if LYNPARZA showed clinical benefit, a formal analysis was performed of the overall trial population of men with HRRm genes.

Merck presents results from Phase 3 KEYNOTE-426 study, Stockwinners
AstraZeneca and Merck report prostate cancer , Stockwinners

Results showed a statistically-significant and clinically-meaningful improvement with LYNPARZA in the primary endpoint of radiographic progression-free survival in BRCA1/2 or ATM-mutated tumors reducing the risk of disease progression or death by a median of 7.4 months versus 3.6 months for those receiving abiraterone or enzalutamide.

LYNPARZA reduced the risk of disease progression or death by 66% for these men. The trial also met the key secondary endpoint of rPFS in the overall HRRm population, where LYNPARZA reduced the risk of disease progression or death by 51% and improved rPFS to a median of 5.8 months vs. 3.5 months for those receiving abiraterone or enzalutamide.

In the key secondary endpoint of time to pain progression, median TTPP was not reached with LYNPARZA and was 9.92 months with abiraterone and enzalutamide in patients with BRCA1/2 or ATM mutations.

Results also showed a trend at this interim analysis time point for improvement in overall survival, another key secondary endpoint. LYNPARZA extended OS to a median of 18.5 months versus 15.1 months for abiraterone or enzalutamide in men with BRCA1/2 or ATM-mutated tumors, of which 81% started on abiraterone or enzalutamide and, following confirmed disease progression, then switched to LYNPARZA.

At this interim analysis, the OS endpoint did not meet statistical significance. In an exploratory analysis, a similar trend in OS was observed at this interim analysis in the HRRm population with a median of 17.5 months for men treated with LYNPARZA vs. 14.3 months for those receiving abiraterone or enzalutamide.

The trial showed a confirmed overall response rate a key secondary endpoint of 33.3% for LYNPARZA vs. 2.3% for abiraterone or enzalutamide in patients with BRCA1/2 or ATM mutations.

In an exploratory analysis of patients in the overall HRRm population, confirmed ORR was 21.7 % for LYNPARZA vs. 4.5% for patients receiving abiraterone or enzalutamide. The safety and tolerability profile of LYNPARZA in the PROfound trial was in line with that observed in prior clinical trials.

The most common adverse events greater than or equal to20% for LYNPARZA compared to abiraterone or enzalutamide were anemia, nausea, fatigue and asthenia, decreased appetite, and diarrhea. Grade 3 or above AEs were anemia, fatigue and asthenia, vomiting, dyspnea, urinary tract infection, nausea, decreased appetite, diarrhea, and back pain. AEs led to discontinuation of treatment in 16% of patients on LYNPARZA vs. 9% on abiraterone and enzalutamide.

AstraZeneca and Merck are also exploring additional trials in prostate cancer, including the ongoing Phase 3 PROpel trial, evaluating LYNPARZA as a first-line therapy in mCRPC for patients with or without HRR mutations, in combination with abiraterone acetate.

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Advaxis jumps on its prostate cancer drug data

Advaxis says ADXS-PSA in combination with KEYTRUDA prolonged survival in mCRPC

Advaxis jumps on its prostate cancer drug data, Stockwinners

Advaxis (ADXS) announced updated data from the Phase 1/2 KEYNOTE-046 study in metastatic, castration-resistant prostate cancer.

Castrate-resistant prostate cancer refers to prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels. Many early-stage prostate cancers need normal levels of testosterone to grow, but castrate-resistant prostate cancers do not. 

Androgens are required for normal growth and function of the prostate. Androgens are also necessary for prostate cancers to grow. Androgens promote the growth of both normal and cancerous prostate cells by binding to and activating the androgen receptor, a protein that is expressed in prostate cells Once activated, the androgen receptor stimulates the expression of specific genes that cause prostate cells to grow .

Early in their development, prostate cancers need relatively high levels of androgens to grow. Such prostate cancers are called castration sensitive, androgen dependent, or androgen sensitive because treatments that decrease androgen levels or block androgen activity can inhibit their growth.

This trial is being conducted in conjunction with Merck (MRK) and is evaluating ADXS-PSA, one of Advaxis’ Listeria monocytogenes-based immunotherapies, alone and in combination with KEYTRUDA, Merck’s anti-PD-1 therapy.

Findings will be highlighted in a poster discussion entitled “Effects of ADXS-PSA with or without Pembrolizumab on Survival and Antigen Spreading in Metastatic, Castration-Resistant Prostate Cancer Patients” at the American Association for Cancer Research Annual Meeting underway in Atlanta.

KEYNOTE-046 is an open-label, multicenter, dose-determining safety and tolerability Phase 1/2 trial of 50 heavily pretreated patients conducted in two parts, with a Phase 2 expansion cohort. The objective of the study is to evaluate ADXS-PSA alone and in combination with KEYTRUDA for primary endpoints that include safety, tolerability and dosing.

Secondary endpoints include anti-tumor activity and progression-free survival, and exploratory endpoints include associations between biomarkers of immunologic response with clinical outcomes.

Key findings from the combination arm of KEYNOTE-046 include the following: The majority of treatment-related adverse events consisted of transient and reversible Grade 1-2 chills/rigors, fever, hypotension, nausea and fatigue.

The combination of ADXS-PSA and pembrolizumab has been well-tolerated, to date, with no additive toxicity observed. Median overall survival was 21.1 months at data cutoff in this dataset of 37 patients.

Correlative immune analyses showed T-cell responses against PSA in 75% of subjects and antigen spreading in 85% of subjects. Broader immune stimulation, including B-cell activation, was observed in the combination arm than in the ADXS-PSA monotherapy arm.

ADXS closed at $5.91, it last traded at $8.15. MRK closed at $83.17.

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