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

Phase 2RecruitingNCT07540572

IDEAYA Biosciences160 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Interventions

IDE574DRUG

IDE574

Fulvestrant injectionDRUG

Fulvestrant Injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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)

Locations (10)

START Astera, LLC

East Brunswick, New Jersey, United States

RECRUITING

START New York Long Island, LLC

Lake Success, New York, United States

RECRUITING

NEXT Texas LLC - Austin

Austin, Texas, United States

RECRUITING

NEXT Texas LLC - Dallas

Dallas, Texas, United States

RECRUITING

START Dallas Fort Worth, LLC

Fort Worth, Texas, United States

RECRUITING

NEXT Texas LLC - Houston

Houston, Texas, United States

RECRUITING

NEXT Texas LLC - San Antonio

San Antonio, Texas, United States

RECRUITING

Start San Antonio, LLC

San Antonio, Texas, United States

RECRUITING

START Mountain Region, LLC

West Valley City, Utah, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, United States

RECRUITING

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

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 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: 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: Time Frame: Approximately 24 months total study duration

Secondary Outcomes

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

Time frame: 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

Time frame: 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.

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: Approximately 24 months total study duration

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation

Maximum observed concentration (Cmax)

Time frame: Approximately 24 months total study duration

Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation

Time to maximum observed concentration (Tmax)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Approximately 24 months total study duration

Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion

Maximum observed concentration (Cmax)

Time frame: Approximately 24 months total study duration

Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion

Time to maximum observed concentration (Tmax)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: Approximately 24 months total study duration

Evaluate the PK of IDE574 in Part 2A Combination Dose Escalation

Maximum observed concentration (Cmax)

Time frame: Approximately 24 months total study duration

Evaluate the PK of IDE574 in Part 2A Combination Dose Escalation

Time to maximum observed concentration (Tmax

Time frame: 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)

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: Approximately 24 months total study duration

Evaluate the PK of IDE574 in Part 2B Combination Dose Expansion

Maximum observed concentration (Cmax)

Time frame: Approximately 24 months total study duration

Evaluate the PK of IDE574 in Part 2B Combination Dose Expansion

Time to maximum observed concentration (Tmax)

Time frame: 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)

Time frame: Approximately 24 months total study duration

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

Overview

Conditions

Interventions

Eligibility

Locations (10)

Outcomes

Primary Outcomes

Secondary Outcomes