ASCO: Pfizer’s TALA (talazoparib)

Pfizer’s TALA (talazoparib) in metastatic castration-resistant prostate cancer (mCRPC)

ASCO 20 Virtual is happening from May 29 - 31st, and it is interesting to watch major Oncology Pharma companies and their key presentations.

Pfizer is worth mentioning here, as it is presenting key posters and studies on talazoparib in metastatic castration-resistant prostate cancer (mCRPC) treatment.

Talazoparib History:

Talazoparib, originally a BioMarin drug before being sold to Medivation in 2015 is now Pfizer’s asset after it acquired Medivation in 2017 for a $14 billion business deal.

Talazoparib Facts:

According to industry-experts, Talazoparib is a PARP inhibitor. PARP inhibitors halt prostate cancer cell (DNA Deficient Repair Protein Prostate Cancer Cells) from repairing the DNA. But talazoparib traps PARP on the DNA (unique to talazoparib), so it does not have to rely on underlying DNA repair deficiency inside the cancer cells. When Enzalutamide is administered to the patients who have progressive CRPC, cancer cells increasingly rely on PARP to survive, and PARP becomes essential for the survival of prostate cancer cells when they are being killed by enzalutamide, and at this time, talazoparib is used to deactivate and trap PARP.

Talazoparib Approval History:

Talazoparib (TALZENNA, Pfizer Inc.), approved in Oct 2018 by FDA, is a poly (ADP-ribose) polymerase (PARP) inhibitor, for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative locally advanced or metastatic breast cancer.

Enzalutamide (XTANDI, Astellas Pharma Inc.) was approved in Dec 2019 by FDA, in patients with metastatic castration-sensitive prostate cancer (mCSPC). Enzalutamide is a competitive androgen receptor inhibitor that affects multiple stages of the signaling pathway.

Key abstracts/Posters:
#Abstract TPS5598

TALAPRO-2, is a Phase III, a 2-part study evaluating the efficacy, safety, pharmacokinetics, and patient-reported outcomes (PROs) of TALA (Talazoparib) combined with ENZA (Enzalutamide) for patients with first-line metastatic castration-resistant prostate cancer (mCRPC).

This study compares rPFS (Radiographic Progression-Free Survival) in men with mCRPC treated with talazoparib plus enzalutamide vs. enzalutamide after confirmation of the starting dose of talazoparib in combination with enzalutamide.

#Poster 5566

Interim Aanlysis (IA) of TALAPRO-1, a Phase II study of talazoparib (TALA) in patients with DNA damage repair alterations (DDRm) and metastatic castration-resistant prostate cancer (mCRPC).

TALAPRO-1 study is assessing the efficacy and safety of talazoparib in men with DNA repair defects metastatic castration-resistant prostate cancer (CRPC) who previously received taxane-based chemotherapy and progressed on at least 1 novel hormonal agent (enzalutamide and/or abiraterone acetate/prednisone).

Results show that TALA monotherapy has shown encouraging antitumor activity in docetaxel-pretreated mCRPC pts with BRCA1/2 alterations and was generally well tolerated.

#Abstract 5515

PROSPER, a phase III, randomized, double-blind, placebo (PBO) controlled study of enzalutamide (ENZA) in men with non-metastatic castration-resistant prostate cancer (nmCRPC) for final overall survival.