NCT03611868

A Study of APG-115 in as a Monotherapy or Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors

A Phase Ib/II Study of APG-115 as a Monotherapy or in Combination With Pembrolizumab in Patients With Unresectable or Metastatic Melanomas or Advanced Solid Tumors

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 230 (estimated)
• Sponsor: Ascentage Pharma Group Inc. · Industry
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

This study aims to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of APG-115, an MDM2 inhibitor, either alone or in combination with pembrolizumab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with metastatic melanomas or advanced solid tumors. Our hypothesis is that restoration of the immune response concomitant to inhibition of the MDM2 pathway (which restores p53 functions) may promote cancer cell death, leading to effective anticancer therapy.

Detailed description

This is a phase I/II study to assess the safety and tolerability of APG-115 alone or in combination with pembrolizumab in patients with unresectable or metastatic melanoma, NSCLC, solid tumors with ATM mutation, liposarcoma, urothelial carcinomas, and malignant peripheral nerve sheath tumors (MPNST)The hypothesis is that the current therapy may improve ORR, progression-free survival, and synergistic effect of APG-115 alone or in combination with pembrolizumab in these patients. (n=230, ID: NCT03611868).

Conditions

• Unresectable or Metastatic Melanoma or Advanced Solid Tumors
• Melanoma
• Uveal Melanoma
• P53 Mutation
• MDM2 Gene Mutation
• Cutaneous Melanoma
• Mucosal Melanoma
• Malignant Peripheral Nerve Sheath Tumors (MPNST)

Interventions

Type	Name	Description
DRUG	Phase 1b: APG-115+pembrolizumab	dose escalation of APG-115 in combination with label dose of pembrolizumab, Four dose levels of APG-115 will be tested: 50, 100, 150, and 200 mg. APG-115 will be administrateddose escalation of APG-115 in combination with label dose of pembrolizumab, Fourfour dose levels of APG-115 will be tested: 50, 100, 150, and 200 mg. APG-115 will be administrated orally every other day (QOD) for consecutive 2 weeks (ie. dosed at Day 1, 3, 5, 7, 9, 11, and 13), with one week dosing off as there are cycles every 3-weeks a cycle. Pembrolizumab is administrated following FDA approved label dose, i.e., 200 mg intravenous infusion at Day 1 of every 3 weeks as a cycle. Phase II: Combination of APG-115 at 150 mg (RP2D) and pembrolizumab or APG-115 monotherapy alone.

Timeline

• Start date: 2018-08-29
• Primary completion: 2025-12-30
• Completion: 2025-12-30
• First posted: 2018-08-02
• Last updated: 2025-08-07

Locations

21 sites across 2 countries: United States, Australia

Regulatory

• FDA-regulated drug study