Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC

Conditions

• Adenoid Cystic Carcinoma
• Advanced Solid Tumor
• Cervical Cancer
• Esophageal Cancer
• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Metastatic Breast Cancer
• Metastatic Colorectal Cancer
• Metastatic Head and Neck Carcinoma
• Metastatic Melanoma
• Metastatic Prostate Cancer
• Metastatic Renal Cell Carcinoma
• Non Small Cell Lung Cancer
• Ovarian Cancer
• Pancreas Cancer
• Salivary Gland Cancer
• Sarcomas
• Small Cell Lung Cancer
• Urothelial Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• ONC-392 — DRUG
  ONC-392 will be given by intravenous infusion, once every 21 days (Q3W). In Part C Arm M and in Part D, ONC-392 will be given Q4W.
• Pembrolizumab — DRUG
  Pembrolizumab will be given intravenous (IV) infusion at 200 mg/cycle, once every 21 days (Q3W).
• Docetaxel — DRUG
  Docetaxel will be given intravenous (IV) infusion at 75 mg/m2, once every 21 days (Q3W).

Study Details

This is a First-in-Human Phase IA/IB/II open label dose escalation study of intravenous (IV) administration of ONC-392, a humanized anti-CTLA4 IgG1 monoclonal antibody, as single agent and in combination with pembrolizumab in participants with advanced or metastatic solid tumors and non-small cell lung cancers.

Key Dates

Start date

Sep 16, 2020

Status verified

May 2025

Primary completion

Jun 30, 2026

Completion

Dec 31, 2027

Study Design

Enrollment

733 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: ONC-392 Treatment as single agent
  The Part A study will test ONC-392 intravenous (IV) infusion up to five predefined dose levels from 0.1 mg/kg to 10 mg/kg ONC-392 as monotherapy every 21 days (Q3W). The Part A study will determine the maximal tolerable dose (MTD) and the recommended Phase 2 dose in monotherapy (RP2D-M). In Part C, Arms A-C, I-N monotherapy expansion cohorts will further assess the safety and efficacy of ONC-392 in different dose levels as monotherapy in pancreatic cancer, triple negative breast cancer, non small cell lung cancer with driver mutations, PD-1 resistant non small cell lung cancer, PD-1 resistant melanoma, head and neck cancer, ovarian cancer, renal cell carcinoma and other solid tumors. Part D is a Phase II study on recurrent and/or metastatic adenoid cystic carcinoma.
• Experimental: ONC-392 in combination with pembrolizumab
  The Part B1 study will test ONC-392 intravenous (IV) infusion, Q3W, in combination with fixed dose of pembrolizumab. The dose for pembrolizumab will be fixed at 200mg/cycle dosed every 21 days (Q3W). The Part B1 will start at one level below RP2D-M dose for ONC-392 and 200mg of pembrolizumab. When 2 DLTs occur before 6 patients are enrolled, the ONC-392 dose will be decreased to the next dose level until ≤ 1/6 patients treated at that dose develops a DLT. This dose level will be designated RP2D-C. In Part C, the expansion cohorts Arm D to G will assess the safety and efficacy of ONC-392 in different dose levels and Pembrolizumab combination therapy in non small cell lung cancer, and metastatic melanoma.
• Experimental: ONC-392 and docetaxel
  Part E Arm O will test ONC-392 in combination with docetaxel, IV infusion, Q3W, in PD-1 resistant NSCLC patients.

Primary Outcome Measure

Dose limiting toxicity (DLT) in monotherapy [ Time Frame: 21 days ]

Locations (33)

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