gotistobart (BNT316) / OncoC4, BioNTech - LARVOL DELTA

BioNTech and OncoC4 Announce Clinically Meaningful Overall Survival Benefit for Selective Treg Modulator Gotistobart in Patients with Previously Treated Squamous Non-Small Cell Lung Cancer (GlobeNewswire) - "Data from the non-pivotal stage of the trial are being presented today in an oral presentation at the IASLC ASCO 2025 North America Conference on Lung Cancer....At the data cut-off on August 8, 2025, 87 patients with sqNSCLC had been randomized....At a median follow-up of 14.5 months, patients in the gotistobart treatment arm had not yet reached the median OS, while the docetaxel treatment arm achieved a median OS of 10 months. The data showed that the gotistobart arm reduced the risk of death by 54% compared to the docetaxel treatment arm (HR=0.46, 95% CI: 0.25–0.84; nominal p-value 0.0102)."

P3 data • Non Small Cell Lung Cancer

PRESERVE-006: ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC (clinicaltrials.gov) - P1/2 | N=148 | Active, not recruiting | Sponsor: OncoC4, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

OncoC4 announced…that China's National Medical Product Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for gotistobart (BNT316/ONC392) for the treatment of patients with squamous non-small cell lung cancer (sqNSCLC) who have progressed on prior standard immuno-oncology therapies (IO) (PRNewswire) - "The NMPA's BTD designation is based on the Stage 1 safety and efficacy data of the PRESERVE-003 trial. The detailed data will be reported in an upcoming medical conference in December 2025."

Breakthrough therapy • P3 data • Lung Non-Small Cell Squamous Cancer

PRESERVE-003: A Phase 3 Study of Gotistobart Versus Docetaxel in Metastatic NSCLC After Progression on PD-(L)1 Inhibitors (IASLC-WCLC 2025) - P3 | "While CTLA-4 is a recognized immunotherapy target in solid tumors, no current anti-CTLA-4 antibodies, including ipilimumab and tremelimumab have demonstrated efficacy as monotherapies to date in NSCLC. Kaplan-Meier estimates of median OS will be presented by treatment arm, along with two-sided 95% CIs. Secondary endpoints include objective response rate and progression-free survival based on RECIST 1.1, and safety."

IO biomarker • Metastases • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Solid Tumor • PD-1

Trial Design for Next-Generation CTLA-4 Antibody Gotistobart Monotherapy Being Co-Developed with BioNTech in NSCLC at the IASLC 2025 World Conference on Lung Cancer (GlobeNewswire) - "The presentation will feature the pivotal trial Stage II design for PRESERVE-003 (NCT05671510), a two-stage, randomized, open-label, active-controlled Phase 3 Study evaluating gotistobart monotherapy compared to docetaxel in squamous non-small cell lung cancer (sqNSCLC) after progression on a PD-(L)1 inhibitor."

Clinical protocol • Lung Non-Small Cell Squamous Cancer

PRESERVE-004: ONC-392 and Pembrolizumab in Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P2 | N=58 | Active, not recruiting | Sponsor: OncoC4, Inc. | Trial primary completion date: Jun 2025 ➔ Oct 2025

Platinum resistant • Trial primary completion date • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Phase 3, Two-stage, Randomized Study of ONC-392 Versus Docetaxel in Metastatic Non-Small Cell Lung Cancers that Progressed on PD-1/PD-L1 Inhibitors (ChiCTR) - P3 | N=600 | Recruiting | Sponsor: Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LAG3 • TIGIT

Gotistobart in combination with pembrolizumab in patients with advanced melanoma who have progressed on PD-1 inhibitors with or without CTLA-4 inhibitors. (ASCO 2025) - P1/2 | "Gotistobart is a pH-sensitive anti-CTLA-4 mAb and we hypothesized that gotistobart in combination with pembrolizumab (pembro) could improve outcomes for ipilimumab plus nivolumab (ipi/nivo) treatment failure. Gotistobart 3 mg/kg or 6 mg/kg plus pembro 200 mg, Q3W, provided durable response and clinically meaningful OS benefit, regardless of prior ipi treatment, with nearly half of patients being next-treatment free at one year follow up. To our knowledge, this is one of the largest cohorts ever studied in patients with advanced melanoma R/R to ipi/nivo."

Clinical • Combination therapy • IO biomarker • Metastases • Gastroenterology • Gastrointestinal Disorder • Immunology • Melanoma • Oncology • Solid Tumor • BRAF

Phase 1 study of gotistobart (BNT316/ONC-392) in combination with lutetium Lu 177 vipivotide tetraxetan (Lu 177) in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2025) - P1/2 | "With known limitations in sample size during dose escalation, gotistobart in combination with Lu 177 demonstrated a manageable safety profile and promising preliminary PSA50 rates in patients with mCRPC during the dose escalation phase. Overall findings support combination regimens with gotistobart doses less than 10 mg/kg in the ongoing Phase 2 randomized dose optimization study."

Clinical • Combination therapy • Metastases • P1 data • Castration-Resistant Prostate Cancer • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Immunology • Oncology • Prostate Cancer • Solid Tumor

Early Results Show Improved Survival Rates in Patients with Metastatic Prostate Cancer (NYU Langone Health) - P1/2 | N=141 | PRESERVE-006 (NCT05682443) | Sponsor: OncoC4, Inc. | "The early findings from 24 patients showed the drug combination was generally well tolerated, with most side effects rated as mild to moderate. Trial participants who received lower doses saw promising reductions in PSA levels—a key marker of prostate cancer activity—suggesting the treatment may be effective. These results support moving forward with a phase 2 trial to optimize dosing and further evaluate benefits for patients."

P1 data • Prostate Cancer

BioNTech to Present Progress Across Diversified Oncology Pipeline at the 2025 ASCO Annual Meeting (The Manila Times) - "Preliminary data on BNT316/ONC-392 (gotistobart)...from two ongoing Phase 1/2 clinical trials evaluating the antibody candidate in combination with current standard of care treatments will be presented. Data from the PRESERVE-001 clinical trial...in patients with advanced melanoma indicated a manageable safety profile and early signs of anti-tumor activity....Data from the PRESERVE-006 clinical trial...in patients with metastatic CRPC indicated a manageable safety profile and preliminary efficacy."

P1/2 data • Castration-Resistant Prostate Cancer • Melanoma

PRESERVE-001: Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC (clinicaltrials.gov) - P1/2 | N=733 | Active, not recruiting | Sponsor: OncoC4, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Adenoid Cystic Carcinoma • Breast Cancer • Cervical Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Salivary Gland Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer

LuCa-MERIT-1: Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: BioNTech SE | N=160 ➔ 220 | Trial completion date: Nov 2028 ➔ Nov 2031 | Trial primary completion date: Apr 2027 ➔ Feb 2030

Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

PRESERVE-009: Safety, PK and Efficacy of AI-061 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: OncoC4, Inc. | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Anal Carcinoma • Biliary Cancer • Bladder Cancer • Cervical Cancer • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • High Grade Serous Ovarian Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Morgan Stanley: Personalized cancer vaccines and ADCs will become the main catalysts for the tumor treatment industry in 2025 [Google translation] (Sina Corp) - "It is reported that in a mid-term trial of patients with surgically resected high-risk melanoma (stage III/IV), Moderna's personalized cancer vaccine mRNA-4157 (V940) combined with Merck's PD-1 inhibitor Keytruda can improve patient survival and show lasting efficacy. Morgan Stanley analyst Terence Flynn pointed out that Moderna is waiting for the key phase II interim data of this melanoma combination therapy in the fourth quarter of 25/26...BioNTech is expected to release updated Phase 3 data from its anti-CTLA-4 candidate BNT316 in NSCLC....In terms of anti-tigit therapy, Merck is waiting for phase 3 data on MK-7684A as a first-line combination therapy for non-small cell lung cancer..."

Clinical data • Melanoma • Non Small Cell Lung Cancer

PRESERVE-003: ONC-392 Versus Docetaxel in Metastatic NSCLC That Progressed on PD-1/PD-L1 Inhibitors (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: OncoC4, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTLA4 • LAG3 • TIGIT

PRESERVE-004: ONC-392 and Pembrolizumab in Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P2 | N=58 | Active, not recruiting | Sponsor: OncoC4, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

PRESERVE-003: ONC-392 Versus Docetaxel in Metastatic NSCLC That Progressed on PD-1/PD-L1 Inhibitors (clinicaltrials.gov) - P3 | N=600 | Active, not recruiting | Sponsor: OncoC4, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTLA4 • LAG3 • TIGIT

Late-Breaking Abstract: A PHASE 2 RANDOMIZED DOSE OPTIMIZATION TRIAL OF GOTISTOBART, A PH-SENSITIVE ANTI-CTLA-4, IN COMBINATION WITH PEMBROLIZUMAB IN PLATINUM-RESISTANT OVARIAN CANCER (PROC, PRESERVE-004/GOG-3081; NCT05446298) (IGCS 2024) - P2 | "Unconfirmed ORR was 31.8% (7/22; 95% CI 13.9-54.9) and 36.4% (8/22; 95% CI 17.2-59.3) in 1 mg/kg and 2 mg/kg groups, respectively (Table 1). Conclusion/Implications Early results show encouraging safety and clinical activity in PROC patients receiving gotistobart+pembrolizumab."

Clinical • Combination therapy • Late-breaking abstract • P2 data • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

FDA puts partial clinical hold on gotistobart trial (The Pharma Letter) - "The US Food and Drug Administration (FDA) has placed a partial clinical hold on the two-stage, open-label, randomized Phase III trial, PRESERVE-003 (NCT05671510). BioNTech (Nasdaq: BNTX) and partner USA-based OncoC4 understand that the partial clinical hold in the ongoing Phase III trial with BNT316/ONC-392 (gotistobart) in non-small cell lung cancer (NSCLC) is due to varying results between the squamous and non-squamous NSCLC patient populations, the German biotech disclosed in a Securities and Exchange Commission (SEC) filing. BioNTech’s shares dipped 3% to $111.11 on the news....A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results. Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment."

Trial suspension • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer

Gotistobart Plus Pembrolizumab Shows Activity in Platinum-Resistant Ovarian Cancer (OncLive) - P2 | N=58 | NCT05446298 | Sponsor: OncoC4, Inc. | "Findings showed that evaluable patients treated with gotistobart at 1 mg/kg plus pembrolizumab (n = 32) experienced an objective response rate (ORR) of 25.0% (95% CI, 11.5%-43.4%), including a complete response (CR) rate of 3.1% and a partial response (PR) rate of 21.9%....The safety profile was manageable at both dose levels, and no new safety signals were identified with the combination. All of patients in the 1-mg/kg cohort (n = 33) and 96.6% in the 2-mg/kg cohort (n = 29) experienced any-grade treatment-emergent adverse effects (TEAEs). Grade 3 or higher TEAEs occurred in 75.8% and 86.2% of patients in the 1-mg/kg and 2-mg/kg groups, respectively."

P2 data • Ovarian Cancer

A randomized, phase II, dose optimization of gotistobart, a pH-sensitive anti-CTLA-4, in combination with standard dose pembrolizumab in platinum-resistant recurrent ovarian cancer: Safety, efficacy and dose optimization (PRESERVE-004/GOG-3081) (ESMO 2024) - P2 | "Early results show encouraging safety and clinical activity in PROC patients receiving gotistobart + pembrolizumab."

Clinical • Combination therapy • Late-breaking abstract • P2 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer

BioNTech to Present Clinical Data Updates Across mRNA and Immunomodulatory Oncology Portfolio at ESMO Congress 2024 (GlobeNewswire) - "Preliminary data of the randomized Phase 2 clinical trial (NCT05446298) with BNT316/ONC-392 (gotistobart), an investigational anti-CTLA-4 antibody, in combination with pembrolizumab in patients with platinum-resistant recurrent ovarian cancer ('PROC') will be presented in a late-breaking session."

P2 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

PRESERVE-001: Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC (clinicaltrials.gov) - P1/2 | N=733 | Recruiting | Sponsor: OncoC4, Inc. | Trial completion date: Dec 2024 ➔ Dec 2027 | Trial primary completion date: Jun 2024 ➔ Jun 2026

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Adenoid Cystic Carcinoma • Breast Cancer • Cervical Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Salivary Gland Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer

OncoC4 Announces First Patient with Advanced Prostate Cancer Dosed in Phase 1/2 Trial of BioNTech-partnered BNT316/ONC-392 Program (GlobeNewswire) - "OncoC4, Inc...today announced that the first patient with metastatic castration resistant prostate cancer ('mCRPC') has been dosed in a Phase 1/2 trial evaluating the anti-CTLA-4 antibody candidate BNT316/ONC-392 (gotistobart) in combination with radioligand therapy, lutetium (¹⁷⁷Lu) vipivotide tetraxetan (Pluvicto). BNT316/ONC-392 is being jointly developed by BioNTech and OncoC4....The open label, randomized Phase 1/2 trial, PRESERVE-006 (NCT05682443), will assess the safety and efficacy of BNT316/ONC-392 in combination with lutetium (¹⁷⁷Lu) vipivotide tetraxetan in patients with mCRPC who have progressed on an androgen receptor ('AR') pathway inhibitor. The OncoC4-sponsored trial is expected to enroll 144 patients across 20 sites within the United States."

Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor