On June 29, 2023 BioNTech SE (Nasdaq: BNTX, "BioNTech") and OncoC4, Inc. ("OncoC4") reported that the first patient with non-small cell lung cancer (NSCLC) has been treated in a pivotal Phase 3 trial evaluating the companies’ next-generation anti-CTLA-4 antibody candidate BNT316/ONC-392 (gotistobart) (Press release, BioNTech, JUN 29, 2023, View Source [SID1234632954]). The trial is part of BioNTech’s strategy to initiate multiple pivotal trials in 2023 and 2024.

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The two-stage, open-label, randomized Phase 3 trial, PRESERVE-003 (NCT05671510), will assess the efficacy and safety of BNT316/ONC-392 as monotherapy compared to the standard-of-care chemotherapy (docetaxel) in patients with metastatic NSCLC that progressed under previous PD-(L)1-inhibitor treatment. Approximately 600 patients are planned to be enrolled at clinical sites in the United States, Europe and other countries and regions, including Belgium, Germany, Italy, Spain, and Türkiye. The primary endpoint measure will be overall survival. Secondary endpoints include overall response rate, progression-free survival and adverse event profile. The program received Fast Track Designation from the U.S. Food and Drug Administration (FDA) in 2022 and represents an innovative approach which aims to leverage the full potential of CTLA-4-targeting therapies.

"We believe this investigational treatment has the potential to become a new option for patients with late-stage NSCLC who have an otherwise poor prognosis. Given its specific mode of action, this treatment approach may also be applicable in a synergistic combination with other immunotherapeutic modalities to provide benefit to further patient populations," said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. "We are committed to rapidly advancing our oncology pipeline towards late-stage development for multiple product candidates in cancer indications with high unmet medical need."

"Today represents a significant landmark for the differentiated program we developed with BNT316/ONC-392, aiming to overcome current challenges of CTLA-4-targeting cancer therapeutics and in particular the very narrow therapeutic window that restricts them from delivering on their full potential," said Pan Zheng, M.D., Ph.D., Chief Medical Officer and Co-Founder at OncoC4. "With less than three years from first-in-human dosing to Phase 3 initiation, we are hopeful these results will build on the responses we have seen so far."

The initiation of the Phase 3 trial is based on positive safety and efficacy data from an ongoing Phase 1/2 study (NCT04140526) with BNT316/ONC-392 alone and in combination with pembrolizumab in patients with advanced solid tumors. Follow-up data recently presented at the ASCO (Free ASCO Whitepaper) 2023 Annual Meeting demonstrate an encouraging anti-tumor activity and a manageable safety profile for BNT316/ONC-392 in a patient cohort with metastatic, anti-PD-(L)1-resistant NSCLC.

The Phase 3 trial initiation marks the first landmark of BioNTech’s and OncoC4’s strategic collaboration initiated in March 2023. Under the terms of the collaboration agreement, OncoC4 received a $200 million upfront payment and is eligible to receive development, regulatory and commercial milestone payments as well as double-digit tiered royalties. BioNTech and OncoC4 will jointly develop BNT316/ONC-392 as monotherapy and in combination with anti-PD-(L)-1 antibodies in a range of solid tumor indications until regulatory authorization, with the parties equally sharing development costs for such studies. Combinations outside of PD-1 inhibition, in particular all combinations with a compound in BioNTech’s pipeline, will be solely developed by BioNTech. BioNTech will hold the exclusive worldwide commercialization rights for any of these products with participation of OncoC4 in certain markets to be negotiated in the future.

About BNT316/ONC-392 (gotistobart)
BNT316/ONC-392 (gotistobart) is a next-generation anti-CTLA-4 antibody candidate jointly developed by BioNTech and OncoC4. BNT316/ONC-392 is currently in late-stage clinical development as monotherapy or combination therapy in various cancer indications. The immune checkpoint receptor CTLA-4 inhibits T cell immune response and reduces the activity of T cells in recognizing and eliminating cancer cells1. This mechanism is also exploited by cancer cells to prevent them from being eliminated by T cells2. Blocking CTLA-4 may help to preserve T cell activity and enhance anti-tumor activity. BNT316/ONC-392 was designed with the aim to address this mechanism while preserving CTLA-4 recycling and thus the immunosuppressive T cell (regulatory T cells, or "Tregs") function in the peripheral tissues. This approach, which is currently in clinical evaluation, aims to give rise to fewer immune-related adverse effects and a more favorable safety profile. BNT316/ONC-392 is currently being evaluated in an ongoing Phase 1/2 trial, PRESERVE-001, (NCT04140526) in patients with advanced solid tumors as single agent or in combination with pembrolizumab. An ongoing registrational Phase 3 trial, PRESERVE-003 (NCT05671510) evaluates the candidate as monotherapy in patients with metastatic, immunotherapy-resistant non-small cell lung cancer (NSCLC). In addition, the candidate is also being evaluated in a Phase 2 trial as a combination therapy with pembrolizumab in platinum-resistant ovarian cancer (NCT05446298).

About NSCLC
Non-small cell lung cancer (NSCLC) covers all epithelial lung cancers other than small cell lung cancer and includes squamous cell carcinoma, large cell carcinoma, and adenocarcinoma of the lung. It is the most common type of lung cancer, accounting for up to 85% of cases3, with risk factors ranging from smoking to asbestos exposure and pulmonary fibrosis4. With a 5-year relative survival rate of 23% in the United States (2012-2018), NSCLC is a devastating disease with limited treatment options depending on the stage and location of the tumor4. Current standard of care includes surgery, radiotherapy in combination with chemotherapy and immunotherapy