Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion

Ideaya Biosciences

Status and phase: Enrolling; Phase 1

Conditions: Solid Tumor

Treatments: Drug: Paclitaxel; Drug: IDE397; Drug: Docetaxel; Drug: Sacituzumab govitecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT04794699

IDE397-001

Details and patient eligibility

About

This is a Phase 1, open-label, multicenter, dose escalation and expansion study of the safety, PK, PD, and preliminary anti-tumor activity of IDE397 as a single agent and in combination with other anticancer agents including taxanes (docetaxel, paclitaxel), or sacituzumab govitecan (SG), in adult patients with selected advanced or metastatic MTAP-deleted advanced solid tumors who are unresponsive to standard of care therapy. IDE397 is a small molecule inhibitor of methionine adenosyltransferase 2 alpha (MAT2A).

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant must be at least 18 years of age
• Advanced or metastatic solid tumor that has progressed on at least one prior line of treatment or is intolerant to additional effective standard therapy
• Have evidence of homozygous loss of MTAP or MTAP deletion
• Willing to undergo paired fresh biopsy (pre- and post-treatment) procedure. Exceptions may be made for feasibility and safety concerns
• Measurable disease
• ECOG performance status <= 1
• Adequate organ function
• Able to swallow and retain orally administered study treatment
• Recovery from acute effects of prior therapy
• Able to comply with contraceptive/barrier requirements

Exclusion criteria

• Known symptomatic brain metastases
• Known primary CNS malignancy
• Current active liver or biliary disease
• Impairment of gastrointestinal (GI) function
• Active uncontrolled infection
• Clinically significant cardiac abnormalities
• Previous treatment with a MAT2A inhibitor and / or PRMT inhibitor or sacituzumab govitecan
• Systemic anti-cancer therapy or major surgery within 4 weeks prior to study entry
• Radiation therapy within 2 weeks prior to study entry
• Prior irradiation to >25% of the bone marrow
• Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inhibitors or inducers
• Currently receiving another investigational study drug.
• Known or suspected hypersensitivity to IDE397/excipients or components

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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180 participants in 6 patient groups

Part 1: Dose Escalation Monotherapy (Solid Tumors)

Experimental group

Treatment:

Drug: IDE397

Part 2: Monotherapy Dose Expansion (NSCLC, EG and Urothelial)

Experimental group

Treatment:

Drug: IDE397

Part 3: Combination Dose Escalation with docetaxel or paclitaxel (NSCLC, EG and Urothelial)

Experimental group

Treatment:

Drug: Docetaxel

Drug: IDE397

Drug: Paclitaxel

Part 4: Combination Dose Expansion with docetaxel or paclitaxel (NSCLC, EG and Urothelial)

Experimental group

Treatment:

Drug: Docetaxel

Drug: IDE397

Drug: Paclitaxel

Part 5: Combination Dose Escalation with sacituzumab govitecan (SG) (Urothelial)

Experimental group

Treatment:

Drug: Sacituzumab govitecan

Drug: IDE397

Part 6: Combination Dose Expansion with sacituzumab govitecan (SG) (Urothelial)

Experimental group

Treatment:

Drug: Sacituzumab govitecan

Drug: IDE397