Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion

• ClinicalTrials.gov Identifier: NCT04794699
• Recruitment Status: Recruiting
• First Posted: March 12, 2021
• Last Update Posted: May 7, 2024
• Sponsor: IDEAYA Biosciences
• Information provided by (Responsible Party): IDEAYA Biosciences

Tracking Information

• First Submitted Date: March 9, 2021
• First Posted Date: March 12, 2021
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: April 14, 2021
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 3, 2024)

• Dose-limiting Toxicities (DLTs) of IDE397 [ Time Frame: 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 docetaxel or paclitaxel or sacituzumab govitecan [ Time Frame: 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 [ Time Frame: 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 docetaxel or paclitaxel or sacituzumab govitecan [ Time Frame: Approximately 2 years ]
  MTD and RP2D of IDE397 in a combination setting will be determined
• To evaluate preliminary anti-tumor activity of IDE397 in combination expansion arms [ Time Frame: Approximately 2 years ]
  Objective Response Rate (ORR) and Duration of Response (DoR)

Original Primary Outcome Measures (submitted: March 9, 2021)

• Dose-limiting Toxicities (DLTs) of IDE397 [ Time Frame: 21 days following the first dose of IDE397 ]
  Incidence of DLTs of IDE397 will be determined
• Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 [ Time Frame: Approximately 2 years ]
  MTD and RP2D of IDE397 will be determined

Current Secondary Outcome Measures (submitted: May 3, 2024)

• Plasma Pharmacokinetics of IDE397 and metabolite [ Time Frame: Approximately 2 years ]
  Pharmacokinetics of IDE397 and metabolite following single and multiple oral administration as a single agent and in combination with docetaxel or paclitaxel or sacituzumab govitecan, will be determined
• Drug interaction between IDE397 and docetaxel or paclitaxel or sacituzumab govitecan [ Time Frame: Approximately 2 years ]
  Pharmacokinetics of docetaxel or paclitaxel or sacituzumab govitecan.
• Pharmacodynamic effect of IDE397 as a single agent and in combination with docetaxel or paclitaxel or sacituzumab govitecan [ Time Frame: 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 [ Time Frame: 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)

Original Secondary Outcome Measures (submitted: March 9, 2021)

• Plasma Pharmacokinetics of IDE397 and metabolite [ Time Frame: Approximately 2 years ]
  Pharmacokinetics of IDE397 and metabolite following single and multiple oral administration will be determined
• Preliminary anti-tumor activity [ Time Frame: Approximately 2 years ]
  Objective response rate and duration of response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
• Pharmacodynamic effect of IDE397 [ Time Frame: Approximately 2 years ]
  Changes in the levels of MAT2A pathway (SAM and MAT2A) and PRMT5 pathway (SDMA) will be determined

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion
• Official Title: An Open Label, Phase 1, Treatment Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of IDE397 (MAT2A Inhibitor) In Adult Participants With Advanced Solid Tumors
• 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 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor

Intervention

• Drug: IDE397
  IDE397 dosed orally
• Drug: Docetaxel
  Intravenous infusion
• Drug: Paclitaxel
  Intravenous infusion
• Drug: Sacituzumab govitecan
  Intravenous infusion

Study Arms

• Experimental: Part 1: Dose Escalation Monotherapy (Solid Tumors)
  Intervention: Drug: IDE397
• Experimental: Part 2: Monotherapy Dose Expansion (NSCLC, EG and Urothelial)
  Intervention: Drug: IDE397
• Experimental: Part 3: Combination Dose Escalation with docetaxel or paclitaxel (NSCLC, EG and Urothelial)
  Interventions:

  • Drug: IDE397
  • Drug: Docetaxel
  • Drug: Paclitaxel
• Experimental: Part 4: Combination Dose Expansion with docetaxel or paclitaxel (NSCLC, EG and Urothelial)
  Interventions:

  • Drug: IDE397
  • Drug: Docetaxel
  • Drug: Paclitaxel
• Experimental: Part 5: Combination Dose Escalation with sacituzumab govitecan (SG) (Urothelial)
  Interventions:

  • Drug: IDE397
  • Drug: Sacituzumab govitecan
• Experimental: Part 6: Combination Dose Expansion with sacituzumab govitecan (SG) (Urothelial)
  Interventions:

  • Drug: IDE397
  • Drug: Sacituzumab govitecan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 3, 2024): 180
• Original Estimated Enrollment (submitted: March 9, 2021): 40
• Estimated Study Completion Date: March 30, 2027
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: IDEAYA Clinical Trials; +1 650 534 3616; IDEAYAClinicalTrials@ideayabio.com

• Listed Location Countries: Australia, France, Germany, Korea, Republic of, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT04794699
• Other Study ID Numbers: IDE397-001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: IDEAYA Biosciences
• Original Responsible Party: Same as current
• Current Study Sponsor: IDEAYA Biosciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Jasgit Sachdev, MD; IDEAYA Biosciences

• PRS Account: IDEAYA Biosciences
• Verification Date: May 2024