NCT03435250

Study of AG-270 in Participants With Advanced Solid Tumors or Lymphoma With MTAP Loss

A Phase 1 Study of AG-270 in the Treatment of Subjects With Advanced Solid Tumors or Lymphoma With Homozygous Deletion of MTAP

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 123 (actual)
• Sponsor: Institut de Recherches Internationales Servier · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of AG-270 in participants with advanced solid tumors or lymphoma with homozygous MTAP deletion.

Detailed description

The purpose of this Phase 1, multicenter, open-label study is to determine the maximum tolerated dose (MTD) of AG-270, administered as a single agent or in combination with taxane-based chemotherapy, and to characterize its dose-limiting toxicities (DLTs) when given daily by mouth to participants with advanced solid tumors or lymphoma with homozygous deletion of methylthioadenosine phosphorylase (MTAP). In each arm of the study, successive cohorts of participants will receive increasing oral doses of AG-270 to determine the MTD, the dose with maximum pharmacologic activity or the maximum feasible dose, as a single agent and in combination with taxane-based chemotherapy. In the subsequent dose-expansion parts of the study, additional participants in each treatment arm will be treated at the MTD (or one of the described alternative doses) to further characterize that dose's safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD), and to detect preliminary evidence of anti-tumor activity.

Conditions

• Advanced Solid Tumors
• Lymphoma

Interventions

Type	Name	Description
DRUG	AG-270	AG-270, orally, once or twice daily, on Days 1 through 28 of each 28-day cycle, until disease progression or unacceptable toxicity.
DRUG	AG-270	AG-270, orally, once or twice daily, for 1 week prior to the first dose of docetaxel. Thereafter, AG-270 continues to be given daily, on Days 1 through 21 of each 21-day cycle, until disease progression or unacceptable toxicity.
DRUG	AG-270	AG-270, orally, once or twice daily for 1 week prior to the first doses of nab-paclitaxel and gemcitabine. Thereafter, AG-270 continues to be given daily on Days 1 through 28 of each 28-day cycle, until disease progression or unacceptable toxicity.
DRUG	docetaxel	Docetaxel, IV, once during each 21-day cycle, until disease progression or unacceptable toxicity.
DRUG	nab-paclitaxel	Nab-paclitaxel, IV, on Days 1, 8, and 15 of each 28-day cycle, until disease progression or unacceptable toxicity.
DRUG	gemcitabine	Gemcitabine, IV, on Days 1, 8, and 15 of each 28-day cycle, until disease progression or unacceptable toxicity.

Timeline

• Start date: 2018-03-04
• Primary completion: 2023-04-20
• Completion: 2023-04-20
• First posted: 2018-02-19
• Last updated: 2024-07-25

Locations

8 sites across 3 countries: United States, France, Spain

Regulatory

• FDA-regulated drug study