Solid Tumor
Conditions
Keywords
MAT2A, 9p21, CDKN2A, MTAP, Solid Tumors, PRMT5, SAM, Synthetic Lethality, Inhibitor, MTAP deletion, CDKN2A deletion, MAT2A Inhibitor, Advanced solid tumors, Lung Cancer, Bladder Cancer, Squamous, NSCLC, Urothelial Cancer, Non small cell, Sacituzumab govitecan, Trodelvy
Brief summary
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 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).
Interventions
DRUGIDE397
IDE397 dosed orally
DRUGSacituzumab govitecan
Intravenous infusion
Sponsors
IDEAYA Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Active second malignancy or history of another malignancy in the past 2 years * Previous treatment with a MAT2A inhibitor and / or PRMT inhibitor or sacituzumab govitecan * Systemic anti-cancer therapy, therapeutic antibody treatment, or major surgery within 4 weeks prior to study entry * Current radiation-related toxicity or radiation therapy within 2 weeks prior to study entry * Small molecule anti-cancer treatment 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 * Require concomitant use of proton pump inhibitor * Currently receiving another investigational study drug. * Known or suspected hypersensitivity to IDE397/excipients or components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting Toxicities (DLTs) of IDE397 | 21 days following the first dose of IDE397 | Incidence of DLTs of IDE397 will be determined |
| Dose-limiting Toxicities (DLTs) of IDE397 in combination with sacituzumab govitecan | 21 - 28 days following the first dose of IDE397 | Incidence of DLTs of IDE397 in a combination setting will be determined |
| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 | Approximately 2 years | MTD and RP2D of IDE397 will be determined |
| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 in combination with sacituzumab govitecan | Approximately 2 years | MTD and RP2D of IDE397 in a combination setting will be determined |
| To evaluate preliminary anti-tumor activity of IDE397 as monotherapy and in combination with sacituzumab govitecan-hziy in expansion arms | Approximately 2 years | Objective Response Rate (ORR) and Duration of Response (DoR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Pharmacokinetics of IDE397 and metabolite | Approximately 2 years | Pharmacokinetics of IDE397 and metabolite following single and multiple oral administration as a single agent and in combination with sacituzumab govitecan, will be determined |
| Drug interaction between IDE397 and sacituzumab govitecan | Approximately 2 years | Pharmacokinetics of sacituzumab govitecan and relevant catabolism products |
| Pharmacodynamic effect of IDE397 as a single agent and in combination with sacituzumab govitecan | Approximately 2 years | Changes in the levels of MAT2A pathway and PRMT5 pathway will be determined |
| Preliminary anti-tumor activity in IDE397 escalation and combination escalation arms | Approximately 2 years | Objective response rate and duration of response will be assessed by Investigator using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) |
Countries
Australia, France, Germany, South Korea, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORJasgit Sachdev, MD
IDEAYA Biosciences
Outcome results
None listed