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

Official title

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

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.

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.

Interventions

• Drug IDE574
  IDE574
• Drug Fulvestrant injection
  Fulvestrant Injection

Primary outcome measures

• Safety and Tolerability of IDE574 in Part 1 A Monotherapy Dose escalation [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 [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 [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. [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 [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 [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 [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. [Time frame: Time Frame: Approximately 24 months total study duration]

Secondary outcome measures (12)

• Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on the ORR per RECIST version 1.1 [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. [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) [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 [Time frame: Approximately 24 months total study duration]
• Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation [Time frame: Approximately 24 months total study duration]
• Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation [Time frame: Approximately 24 months total study duration]
• Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation [Time frame: Approximately 24 months total study duration]
• Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation [Time frame: Approximately 24 months total study duration]
• Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation [Time frame: Approximately 24 months total study duration]
• Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion [Time frame: Approximately 24 months total study duration]
• Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion [Time frame: Approximately 24 months total study duration]
• Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion [Time frame: Approximately 24 months total study duration]

Eligibility criteria

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

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• Florida Clinical Trials Group — Plantation
• START Astera, LLC — East Brunswick
• START New York Long Island, LLC — Lake Success
• NEXT Texas LLC - Austin — Austin
• NEXT Texas LLC - Dallas — Dallas
• START Dallas Fort Worth, LLC — Fort Worth
• NEXT Texas LLC - Houston — Houston
• NEXT Texas LLC - San Antonio — San Antonio
• … and 3 more centers

Identifiers

NCT: NCT07540572 · IDE574-001 · 178299

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗