A Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of IDE574 Therapy in Adult Participants With Advanced Solid Tumors

An Open Label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of IDE574 as Monotherapy in Locally Advanced or Metastatic Solid Tumors and as Combination Therapy With Fulvestrant in Locally Advanced or Metastatic ER+, HER2- Breast Cancer

IDE574 is a synthetically manufactured small molecule inhibitor that co-targets the lysine acetyltransferase enzymes KAT6 and KAT7.

The purpose of this study is to evaluate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of IDE574 as monotherapy in participants with locally advanced or metastatic solid tumors and as combination therapy with fulvestrant in participants with advanced or metastatic ER+, HER2- breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer (NSCLC); Castration-resistant Prostate Cancer (CRPC); ER+, HER 2- Breast Cancer; Microsatellite Stable (MSS) Colorectal Carcinoma
• Intervention / Treatment: Drug: IDE574; Drug: Fulvestrant injection

Detailed Description

Part 1 - Monotherapy Dose Escalation and Expansion:

Part 1A - Monotherapy Dose Escalation Part 1A will evaluate increasing doses of IDE574 to assess safety, tolerability and to determine dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) or the recommended dose for expansion (RDE) in subjects with advanced or metastatic ER+, HER2- breast cancer, non-small cell lung cancer, castration-resistant prostate cancer and microsatellite-stable colorectal cancer.

Part 1B - Monotherapy Dose Expansion Part 1B will evaluate in ER+ HER2- advanced or metastatic breast cancer at the potential dose level(s) determined to be safe and tolerable during monotherapy dose escalation Part 1A. In parallel, a basket cohort may be enrolled at or below the highest safe dose level(s) determined to be safe and tolerable in Part 1A.

Part 2 - Combination Dose Escalation and Expansion

Part 2A - IDE574 Combination Therapy with Fulvestrant Dose Escalation Part 2A will evaluate participants with ER+ HER2- advanced or metastatic breast cancer with escalating doses of IDE574 in combination with fulvestrant to assess safety, tolerability and to determine DLTs, MTD or RDE.

Part 2B - IDE574 Combination Therapy with Fulvestrant Dose Expansion Part 2B will be evaluated in ER+ HER2- advanced or metastatic breast cancer at the potential dose level(s) determined to be safe and tolerable during combination dose escalation Part 2A.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Recruiting
      • START Astera, LLC
      • Contact: Bruno S Fang; Phone Number: 732-426-4750; Email: info@startresearch.com
  • New York
    • Lake Success, New York, United States, 11042
      • Recruiting
      • START New York Long Island, LLC
      • Contact: Geralinde O'Sullivan Coyne; Phone Number: 363-207-5160; Email: info@startresearch.com
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • NEXT Texas LLC - Austin
      • Contact: Sheena Sahota; Phone Number: 737-610-5200; Email: ssahota@nextoncology.com
    • Dallas, Texas, United States, 75039
      • Recruiting
      • NEXT Texas LLC - Dallas
      • Contact: Farah Polani; Phone Number: 972-893-8800; Email: fpolani@nextoncology.com
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • START Dallas Fort Worth, LLC
      • Contact: Henry Xiong; Phone Number: 682-350-3010; Email: info@startresearch.com
    • Houston, Texas, United States, 77054
      • Recruiting
      • NEXT Texas LLC - Houston
      • Contact: Jennifer Segar; Phone Number: 832-384-7900; Email: jsegar@nextoncology.com
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Start San Antonio, LLC
      • Contact: Amita Patnaik; Phone Number: 2105935250; Email: info@startresearch.com
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Texas LLC - San Antonio
      • Contact: David Sommerhalder; Phone Number: 210-580-9500; Email: dsommerhalder@nextoncology.com
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START Mountain Region, LLC
      • Contact: William B McKean; Phone Number: 1 (801) 907-4750; Email: info@startresearch.com
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia
      • Contact: Mohamad A Salkeni; Phone Number: 703-783-4510; Email: msalkeni@nextoncology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Archival Tissue sample for testing

• Part 1A - Participants with advanced or metastatic ER+, HER2- breast cancer, NSCLC, CRPC, and MSS colorectal adenocarcinoma who have progressed on/after at least one line of standard of care therapy or are intolerant to additional effective therapies.
• Parts 1B, 2A and 2B: Participants with ER+, HER2- breast cancer who have progressed after at least 1 prior line of treatment with an endocrine therapy and a CDK4/6 inhibitor
• Female participants with ER+, HER2- breast cancer considered to be of childbearing potential (or have tubal ligations only) must be willing to undergo medically induced menopause (Parts 2A and B only)
• Female participants of nonchildbearing potential with ER+, HER2- breast cancer must meet at least 1 of the following criteria: Age ≥ 60 years or age <60 years with absence of menstruation for at least 12 months, or had prior removal of both ovaries
• Have Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1.
• Have adequate bone marrow, renal and liver function.
• Life expectancy of >3 months
• Able to safely administer and retain orally administered study treatment
• Able to comply with contraceptive/barrier requirements

Key Exclusion Criteria:

• Known symptomatic brain metastases or leptomeningeal metastasis
• Known primary CNS malignancy and any other malignancies within 2 years prior to the first dose with the exception of adequately treated localized tumor.
• Have impairment of GI function or GI disease that may significantly alter the absorption of IDE574.
• Have active liver or biliary disease.
• Have active, uncontrolled bacterial, fungal, or viral infection
• Have clinically significant cardiac abnormalities and/or blood clotting events within 6 months before the first dose
• If participants had adverse reactions to previous experimental antitumor treatment that have not recovered to Grade ≤ 1
• Prior irradiation to >25% of the bone marrow.
• Known or suspected hypersensitivity to IDE574/excipients or components (Parts 1 & 2) or fulvestrant/excipients or components (Part 2 only)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy Dose Escalation (Part 1A); Participants with the appropriate tumor types will be treated with escalating doses of IDE574	Drug: IDE574; IDE574
Experimental: Monotherapy Dose Expansion (Part 1B); Participants with ER+ HER2- advanced or metastatic breast cancer will be treated using the chosen monotherapy dose(s) of IDE574	Drug: IDE574; IDE574
Experimental: Combination Dose Escalation (Part 2A) IDE574 + Fulvestrant; Participants with ER+ HER2- advanced or metastatic breast cancer will be treated with escalating doses of IDE574 in combination with fulvestrant	Drug: IDE574; IDE574; Drug: Fulvestrant injection; Fulvestrant Injection
Experimental: Combination Dose Expansion (Part 2B); Participants with ER+ HER2- advanced or metastatic breast cancer will be treated using the chosen combination dose(s) of IDE574 + Fulvestrant	Drug: IDE574; IDE574; Drug: Fulvestrant injection; Fulvestrant Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of IDE574 in Part 1 A Monotherapy Dose escalation	incidence of DLT; incidence and severity of AEs/serious adverse events (SAEs) graded based on CTCAE V6.0	21 days following the first dose of IDE574
Safety and Tolerability of IDE574 in Part 1B Monotherapy Dose expansion based on incidence and severity of AEs/SAEs	Incidence and severity of AEs/SAEs graded based on CTCAE V6.0	Approximately 24 months total study duration
To evaluate anti-tumor activity of IDE574 of IDE574 in Part 1B Monotherapy Dose expansion based on the ORR per RECIST version 1.1	Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response	Approximately 24 months total study duration
To evaluate anti-tumor activity of IDE574 of IDE574 in Part 1B Monotherapy Dose expansion based on DOR per RECIST version 1.1.	Duration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response	Approximately 24 months total study duration
Safety and tolerability of IDE574 in combination with Fulvestrant in Part 2A Combination Dose Escalation based on incidence of DLT	Incidence of DLT; incidence and severity of AEs/SAEs graded based on CTCAE V6.0	Approximately 24 months total study duration
Safety and tolerability of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on the incidence and severity of AEs/SAEs	Incidence and severity of AEs/SAEs graded based on CTCAE V6.0	Approximately 24 months total study duration
Anti-tumor activity of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on the ORR per RECIST version 1.1	Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response	Time Frame: Approximately 24 months total study duration
Anti-tumor activity of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on DOR per RECIST version 1.1.	Duration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response	Time Frame: Approximately 24 months total study duration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on the ORR per RECIST version 1.1	Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response	Approximately 24 months total study duration
Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on DOR per RECIST version 1.1.	Duration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response	Approximately 24 months total study duration
Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on Clinical Benefit Rate (CBR)	CBR will be assessed based on the proportion of participants with a Best Overall Response (BOR) of CR, PR or SD lasting for 24 weeks per RECIST version 1.1 from the first dose.	Approximately 24 months total study duration
Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on Disease control rate	Disease Control Rate (DCR) is the proportion of participants with a BOR of CR, PR, and SD lasting for at least 6 weeks (± 7 days) from the first dose per RECIST version 1.1	Approximately 24 months total study duration
Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation	Area under concentration time curve from time 0 to the last quantifiable concentration (AUClast)	Approximately 24 months total study duration
Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation	Area under concentration time curve from time 0 to the end of dosing interval (AUCtau)	Approximately 24 months total study duration
Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation	Maximum observed concentration (Cmax)	Approximately 24 months total study duration
Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation	Time to maximum observed concentration (Tmax)	Approximately 24 months total study duration
Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation	Concentration observed immediately prior to the next dose (Ctrough)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion	Area under concentration time curve from time 0 to the last quantifiable concentration (AUClast)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion	Area under concentration time curve from time 0 to the end of dosing interval (AUCtau)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion	Maximum observed concentration (Cmax)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion	Time to maximum observed concentration (Tmax)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion	Concentration observed immediately prior to the next dose (Ctrough)	Approximately 24 months total study duration
Evaluate antitumor activity of IDE574 in Part 1B Monotherapy Dose Expansion based on CBR for ER+, HER2- breast cancer	CBR will be assessed based on the proportion of participants with a Best Overall Response (BOR) of CR, PR or SD lasting for 24 weeks per RECIST version 1.1 from the first dose	Approximately 24 months total study duration
Evaluate antitumor activity of IDE574 in Part 1B Monotherapy Dose Expansion based on DCR for other solid tumor types	Disease Control Rate (DCR) is the proportion of participants with a BOR of CR, PR, and SD lasting for at least 6 weeks (± 7 days) from the first dose per RECIST version 1.1	Approximately 24 months total study duration
Evaluate the preliminary antitumor activity of IDE574 in combination with Fulvestrant Part 2A Combination Dose Escalation based on ORR per RECIST version 1.1	Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response	Approximately 24 months total study duration
Evaluate the preliminary antitumor activity of IDE574 in combination with Fulvestrant Part 2A Combination Dose Escalation based on DOR per RECIST version 1.1	uration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response	Approximately 24 months total study duration
Evaluate the preliminary antitumor activity of IDE574 in combination with Fulvestrant Part 2A Combination Dose Escalation based on CBR per RECIST version 1.1	CBR will be assessed based on the proportion of participants with a Best Overall Response (BOR) of CR, PR or SD lasting for 24 weeks per RECIST version 1.1 from the first dose.	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2A Combination Dose Escalation	Area under concentration time curve from time 0 to the last quantifiable concentration (AUClast)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2A Combination Dose Escalation	Area under concentration time curve from time 0 to the end of dosing interval (AUCtau)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2A Combination Dose Escalation	Maximum observed concentration (Cmax)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2A Combination Dose Escalation	Time to maximum observed concentration (Tmax	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2A Combination Dose Escalation	Concentration observed immediately prior to the next dose (Ctrough)	Approximately 24 months total study duration
Evaluate antitumor activity of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on CBR per RECIST version 1.1	CBR will be assessed based on the proportion of participants with a Best Overall Response (BOR) of CR, PR or SD lasting for 24 weeks per RECIST version 1.1 from the first dose.	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2B Combination Dose Expansion	Area under concentration time curve from time 0 to the last quantifiable concentration (AUClast)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2B Combination Dose Expansion	Area under concentration time curve from time 0 to the end of dosing interval (AUCtau)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2B Combination Dose Expansion	Maximum observed concentration (Cmax)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2B Combination Dose Expansion	Time to maximum observed concentration (Tmax)	Approximately 24 months total study duration
Evaluate the PK of IDE574 in Part 2B Combination Dose Expansion	Concentration observed immediately prior to the next dose (Ctrough)	Approximately 24 months total study duration

Collaborators and Investigators

• Sponsor: IDEAYA Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2026
• Primary Completion (Estimated): March 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Non-small Cell Lung Cancer (NSCLC); ER+, HER 2- Breast Cancer; Castration-resistant Prostate Cancer (CRPC); Microsatellite Stable (MSS) Colorectal Carcinoma; KAT6A/B; KAT7
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Genetic Diseases, Inborn; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Neurodegenerative Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Heredodegenerative Disorders, Nervous System; Carcinoma, Bronchogenic; Bronchial Neoplasms; Spinal Cord Diseases; Cerebellar Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Spinocerebellar Degenerations; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant
• Other Study ID Numbers: IDE574-001; 178299 (Other Identifier: Regulatory Agency Identifier Number (s))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No