Study launches of BNT316/ONC-392 plus radioligand therapy in mCRPC

The first patient has been dosed in the phase 1/2 PRESERVE-006 trial (NCT05682443), assessing the safety and efficacy of the anti-CTLA-4 antibody candidate BNT316/ONC-392 (gotistobart) in combination with lutetium (¹⁷⁷Lu) vipivotide tetraxetan (Pluvicto) in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on a prior androgen receptor pathway inhibitor, according to a news release by OncoC4, a co-developer of the therapy.¹

Primary completion of the study is planned for June 2026.

This study is a result of a strategic collaboration between OncoC4 and BioNTech, which was announced in March 2023.² The joint collaboration includes the development of BNT316/ONC-392 across a range of solid tumor types, including mCRPC.

“Advances in the treatment of mCRPC have demonstrated improved outcomes, but a high unmet need remains for additional well-tolerated targeted therapies that can further extend survival in these patients. We look forward to evaluating BNT316/ONC-392 in combination with radioligand therapy with the aim to further improve outcomes for patients with this advanced stage of disease,” said principal investigator David R. Wise, MD, PhD, in the news release.¹ Wise is the director of the Perlmutter Cancer Center at NYU Langone Health in New York, New York.

In total, the open-label, randomized phase 1/2 trial is expected to enroll 144 patients across 20 clinical trial sites in the US. The safety and preferred dosage of BNT316/ONC-392 in combination with lutetium (¹⁷⁷Lu) vipivotide tetraxetan will be determined in the phase 1 portion of the study. Phase 2 will further evaluate the safety and efficacy of the combination in patients with mCRPC who have prostate-specific membrane antigen (PSMA)-positive scans, progression on a prior androgen receptor (AR) pathway inhibitor, and are lutetium (¹⁷⁷Lu) vipivotide tetraxetan-naïve.

Inclusion criteria for the study includes having histologically- or cytologically-confirmed metastatic prostate adenocarcinoma, having progressive mCRPC as identified by a serum PSA progression, soft-tissue progression, or progression of bone disease, prior orchiectomy and/or ongoing androgen deprivation therapy, prior treatment with at least 1 second-generation AR-targeting agent, and prior treatment with at least 1, but no more than 2, previous taxane regimens. Additionally, patients must have at least 1 metastatic lesion present on baseline CT, MRI, or bone scan, an ECOG score of 0 or 1, a life expectancy greater than 6 months, adequate organ function, and a positive PSMA PET/CT scan.³

Patients included in the study will be randomly assigned 2:1 to receive eitherBNT316/ONC-392 in combination with lutetium (¹⁷⁷Lu) vipivotide tetraxetan or to standard of care treatment with lutetium (¹⁷⁷Lu) vipivotide tetraxetan. All participants will be dosed with lutetium (¹⁷⁷Lu) vipivotide tetraxetan once every 6 weeks for up to 6 cycles. Those receiving BNT316/ONC-392 will be dosed once every 4 weeks for up to 13 cycles or approximately 1 year.

The primary end point for the study is radiographic progression-free survival with the combination vs the current standard of care. Secondary end points are the objective response rate and the incidence of treatment-emergent/treatment-related adverse events, as well as immune-related adverse events.

Primary completion of the study is planned for June 2026.

References

1. OncoC4 announces first patient with advanced prostate cancer dosed in phase 1/2 trial of BioNTech-partnered BNT316/ONC-392 program. News release. OncoC4, Inc. Published online and accessed February 22, 2024. https://www.oncoc4.com/index.php/blog/news-releases/item/19-oncoc4-announces-first-patient-with-advanced-prostate-cancer-dosed-in-phase-1-2-trial-of-biontech-partnered-bnt316-onc-392-program

2. BioNTech and OncoC4 announce strategic collaboration to co-develop and commercialize novel checkpoint antibody in multiple solid tumor indications. News release. OncoC4. March 20, 2023. Accessed February 22, 2024.

https://www.oncoc4.com/index.php/blog/news-releases/item/14-biontech-and-oncoc4-announce-strategic-collaboration-to-co-develop-and-commercialize-novel-checkpoint-antibody-in-multiple-solid-tumor-indications

3. ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC (PRESERVE-006). ClinicalTrials.gov. Last updated February 8, 2024. Accessed February 22, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05682443