NCT04210037

Study of APG-1252 Plus Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer

A Multi-Center, Phase Ib/II Study of Combination Treatment of APG-1252 With Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Ascentage Pharma Group Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multi-center, open-label, phase Ib/II study of combination therapy with APG-1252 plus paclitaxel in patients with relapsed/refractory small-cell lung cancer(SCLC). The phase Ib portion will be done using time-to-event continual reassessment method (TITE-CRM) methodology to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of APG-1252 with a fixed dose of paclitaxel. The phase II portion will utilize a Simon two-stage design to determine the efficacy of the combination therapy with response rate as the primary endpoint.

Detailed description

Upon enrollment, patients will undergo a comprehensive history and physical exam, along with baseline laboratory assessment. Baseline CT imaging will be required within 4 weeks prior to study entry. Archival tissue is mandatory; a fresh biopsy of the primary tumor or a metastatic lesion prior to initiation of therapy is optional and post-treatment tumor biopsy is strongly encouraged. In the phase Ib portion, eligible patients will receive APG-1252 at the assigned dose-level on days 1, 8 and 15 plus a fixed-dose of paclitaxel 80 mg/m˄2 on days 1 and 8 of a 21-day cycle. There will be three dose-levels of APG-1252 (-1, 80 mg; 1, 160 mg; 2, 240 mg) with the first patient starting at dose-level 1 and subsequent patients at dose-levels determined by the TITE-CRM methodology. There will be no intra-patient dose-escalation. Patients will be continuously assessed for adverse events, including DLTs which are defined in the protocol. Response assessment by CT imaging will occur every 2 cycles and treatment will continue until progression of disease, unacceptable toxicity, patient preference to stop treatment, withdrawal of consent, or administrative discontinuation. In the phase II portion, eligible patients will receive APG-1252 at the RP2D determined in the phase Ib portion on days 1, 8 and 15 plus paclitaxel 80 mg/m˄2 on days 1 and 8 of a 21-day cycle. Response assessment by CT imaging will occur every 2 cycles and treatment will continue until progression of disease, unacceptable toxicity, patient preference to stop treatment, withdrawal of consent, or administrative discontinuation.

Conditions

• Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	APG-1252	APG-1252 (Ascentage Pharma) is a highly potent Bcl-2 family protein inhibitor with high binding affinity for Bcl-2, Bcl-xL and Bcl-w. APG-1252 possesses strong antitumor activity as a single-agent against tumor cells addicted to Bcl-2/Bcl-xL, and exhibits a much broader antitumor activity when combined with chemotherapeutic agents.
DRUG	Paclitaxel	80 mg/m˄2 on days 1 and 8 of a 21-day cycle

Timeline

• Start date: 2020-08-20
• Primary completion: 2021-08-30
• Completion: 2022-05-15
• First posted: 2019-12-24
• Last updated: 2022-07-12

Locations

8 sites across 2 countries: United States, Australia

Regulatory

• FDA-regulated drug study