Convergent Therapeutics and POINT Biopharma Global are partnering in a Phase I/II investigator-initiated trial for men with progressive metastatic castration-resistant prostate cancer (mCRPC). The trial will evaluate the combination of CONV 01-α (225Ac−J591, or rosopatamab-225Ac), Convergent's antibody directed at prostate-specific membrane antigen (PSMA) coupled with Actinium-225 (225Ac), an alpha particle emitter and POINT's PSMA radioligand PNT2002 linked to Lutetium-177 (177Lu), a beta particle emitter.
The study has begun patient accrual and is being conducted at Weill Cornell Medicine with Dr. Scott T. Tagawa, Professor of Medicine and Professor of Medicine in Urology at Weill Cornell Medicine, as Principal Investigator.
The Phase I/II trial is enrolling up to 33 patients with progressive mCRPC who have received a prior androgen receptor signaling inhibitor (ARSI) and taxane chemotherapy and are PSMA PET-positive. The open-label Phase I dose-escalation portion of the study is designed to determine the maximum tolerated dose (MTD) for the combination of CONV 01-α and PNT2002. PNT2002 will be administered at the dose utilized in POINT Biopharma's Phase III SPLASH trial. Escalating doses of CONV 01-α will be administered concurrently, starting with doses previously demonstrated to be well-tolerated. After the Phase I study has established the MTD of the CONV 01-α and PNT2002 combination, investigators will initiate the Phase II expansion study at MTD. The primary objective of the Phase II study is to assess the number of patients who demonstrate a >50% prostate-specific antigen (PSA) decline following treatment.
The co-targeting treatment approach is based on the research of Dr. Neil Bander, the Bernard & Josephine Chaus Professor of Urologic Oncology at Weill Cornell Medicine, who discovered the synergy between radioligands and 225Ac−J591. The finding that antibodies synergistically improve the efficacy of ligand-targeted agents is the subject of patent filings by Cornell University that, in turn, have been exclusively licensed to Convergent Therapeutics, inc. At the ASCO 2021 Annual Meeting in June, Dr. Tagawa presented proof of concept data that demonstrated that a single dose of CONV 01-α had anti-tumor activity in heavily pretreated men with mCRPC.
“Within the field, there is significant and growing interest in our differentiated approach that leverages the complementary advantages of co-targeting surface cancer molecules such as PSMA with both antibodies and small molecule ligands, as well as alpha and beta radiopharmaceuticals. This collaboration with POINT Biopharma will, therefore, help to facilitate and validate our disruptive strategy of combining radioligands and antibodies carrying different payloads, directed at a cancer target, in order to significantly improve the efficacy of radiopharmaceutical therapies. Our long-term goal is to meaningfully improve outcomes in patients with prostate cancer and to leverage this combinatorial platform to treat other cancers. We look forward to evaluating the results once they are available,” stated Dr. Philip Kantoff, Chief Executive Officer of Convergent Therapeutics.
“Combination therapies are a very exciting opportunity in the radiopharmaceutical space, as demonstrated by Dr. Bander's research into combining different radioligand therapies to improve outcomes. To date, PNT2002 has shown promise as a monotherapy and we believe that this collaboration has the potential to not only improve patient outcomes, but also provide patients and physicians with new therapeutic options for advanced prostate cancers,” said Dr. Joe McCann, Chief Executive Officer of POINT Biopharma.Back To Top
Collaboration Will Evaluate Treatment for Progressive mCRPC. Appl Rad Oncol.