IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Advanced Head and Neck Squamous Cell Carcinoma; Advanced Ovarian Clear Cell Adenocarcinoma; Chondrosarcoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8
• Interventions: Drug: Glutaminase-1 Inhibitor IACS-6274; Biological: Bevacizumab; Drug: Capivasertib; Drug: Paclitaxel

• Registration Number: NCT05039801
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

To find the highest tolerable dose of IACS-6274 that can be given alone, in combination with bevacizumab and paclitaxel, or in combination with capivasertib to patients who have solid tumors. The safety and tolerability of the study drug(s) will also be studied.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of oral glutaminase inhibitor IPN60090 (IACS-6274) as monotherapy (Part A) and in combination therapy with bevacizumab and weekly paclitaxel (Part B) and in combination with capivasertib (Part C)

II. To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of IACS-6274 in combination with bevacizumab and weekly paclitaxel (Part B). and of the combination of IACS-6274 and capivasertib (Part C). (For Dose Escalation Only)

SECONDARY OBJECTIVES:

I. To assess the preliminary antitumor activity of IACS-6274 as monotherapy (Part A) in patients with or without biomarker selected tumor types.

II. To assess the preliminary antitumor activity of IACS-6274 in the combination with bevacizumab and weekly paclitaxel (Part B) in patients with recurrent platinum-resistant ovarian cancer and in combination with capivasertib (Part C) for all solid tumors.

III. To characterize the pharmacokinetics (PK) profile of IACS-6274 as a monotherapy (Part A) and in combination with bevacizumab and weekly paclitaxel (Part B) in the combination with capivasertib (Part C). To evaluate biomarkers of patient stratification and correlate them with clinical outcome.

EXPLORATORY OBJECTIVE:

I. To collect biobank samples for potential future analysis of biomarkers (optional, informed consent required).

OUTLINE: This is a dose-escalation study of IACS-6274 followed by a dose-expansion study. Patients are assigned to 1 of 2 parts.

PART A: Patients receive IACS-6274 orally (PO) throughout the study.

PART B: Patients receive IACS-6274 PO, paclitaxel intravenously (IV), and bevacizumab IV throughout the study.

PART C: Patients receive IACS-627 PO, with capivasertib PO throughout the study.

Study Timeline

• Study First Submitted: 2021-09-01
• Study Start: 2021-09-09
• Study First Submitted QC: 2021-09-09
• Study First Posted: 2021-09-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-21
• Last Update Posted: 2025-04-23
• Primary Completion: 2026-05-29
• Study Completion: 2026-05-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A (IACS-6274)	Glutaminase-1 Inhibitor IACS-6274	Patients receive IACS-6274 PO throughout the study.
Part B (IACS-6274, bevacizumab, paclitaxel)	Bevacizumab	Patients receive IACS-6274 PO, paclitaxel IV, and bevacizumab IV throughout the study.
Part B (IACS-6274, bevacizumab, paclitaxel)	Glutaminase-1 Inhibitor IACS-6274	Patients receive IACS-6274 PO, paclitaxel IV, and bevacizumab IV throughout the study.
PART C: (IACS-6274) with capivasertib	Glutaminase-1 Inhibitor IACS-6274	Patients receive IACS-627 PO, with capivasertib PO throughout the study.
Part B (IACS-6274, bevacizumab, paclitaxel)	Paclitaxel	Patients receive IACS-6274 PO, paclitaxel IV, and bevacizumab IV throughout the study.
PART C: (IACS-6274) with capivasertib	Capivasertib	Patients receive IACS-627 PO, with capivasertib PO throughout the study.

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (AEs)	Up to 90 days	Will be assessed by the rate of dose limiting toxicities at each dose level in the dose escalation, and the rate of AEs and the rate of Grade 3 and higher AEs in the dose escalation and dose expansion. All AEs will be coded according to the latest version of Medical Dictionary for Regulatory Activities and National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States