A Study of IDE849 in Patients With DLL3 Expressing Tumors Including Small Cell Lung Cancer

Not Applicable

Recruiting

• Conditions: Small-cell Lung Cancer
• Interventions: Drug: IDE849

• Registration Number: NCT07174583
• Lead Sponsor: IDEAYA Biosciences

Brief Summary

This is Phase 1/2, multicenter, clinical study to evaluate the safety, efficacy, PK, and immunogenicity of IDE849 in subjects with DLL3-expressing tumors including SCLC.

Detailed Description

This study is designed as a multi-stage Phase 1 study within a Phase 2 study.

Phase 1 (Part 1 - Dose Escalation): successive cohorts of subjects will be treated with increasing doses of IDE849 until the maximum tolerated dose (MTD) is reached or the safety of a lower dose(s) is established as per the Bayesian Optimal Interval (BOIN) design.

Phase 2 (Part 2 - Dose Optimization/Expansion): subjects enrolled in Part 2 will be assigned to one of the dose levels being evaluated for dose optimization (at or below the MTD).

Study Timeline

• Status Verified: 2025-09
• Study Start: 2025-09-01
• Study First Submitted: 2025-09-11
• Study First Submitted QC: 2025-09-11
• Last Update Submitted: 2025-09-11
• Study First Posted: 2025-09-16
• Last Update Posted: 2025-09-16
• Primary Completion: 2029-05
• Study Completion: 2029-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Are willing to participate in this clinical study, understand the study procedures, and are able to sign the written ICF.
2. Subjects with histologically or cytologically confirmed SCLC who have radiologically progressed or recurred after previous standard treatment, including platinum-based therapy and programmed death-1/programmed death-ligand 1 inhibitors (except for subjects who refuse or are judged by the Investigator to be unsuitable for immunotherapy). No more than 2 lines of previous systemic chemotherapy in any setting and no more than 3 total lines of systemic therapy in the recurrent or metastatic setting will be allowed.
3. Subjects will be required to provide blood/tumor tissue samples for biomarker testing.
4. Have at least 1 measurable lesion according to RECIST version 1.1.
5. Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
6. Have life expectancy > 3 months.
7. Have adequate bone marrow and organ function.
8. Women of childbearing potential must agree to take highly effective contraceptive measures.

Exclusion Criteria

1. Have mixed SCLC and nonsmall cell lung cancer histology (SCLC with components of large cell neuroendocrine carcinoma are eligible).
2. Subjects with locally untreated (radiotherapy or surgery) or active central nervous system (CNS) tumor metastasis.
3. Have severe cardiovascular and cerebrovascular disease.
4. Have history of clinically significant bleeding within 3 months before the first study dose.
5. Have history of interstitial pneumonitis during previous treatment; current noninfectious pneumonitis requiring steroid therapy; known or suspected interstitial pneumonitis as seen on screening imaging; other moderate to severe lung diseases seriously affecting respiratory function within 3 months before the first dose, including, but not limited to, idiopathic pulmonary fibrosis and organizing pneumonia/obliterative bronchiolitis.
6. Have history of severe infections within 4 weeks prior to the start of study treatment.
7. Have history of immunodeficiency, with a positive human immunodeficiency virus (HIV) test.
8. Subjects with known or suspected viral hepatitis.
9. Have a history of active tuberculosis within 1 year before enrollment.
10. Have received chemotherapy within 4 weeks of first dose of IMP; immunotherapy or biologic targeted antitumor treatments within 2 weeks before the first dose of IMP; for small molecule treatments within 2 weeks before the first dose of the IMP or within 5 half-lives of the drug (whichever is shorter); other investigational products within 4 weeks or within 5 half-lives of the drug (whichever is shorter).
11. Administration of any of the following within 2 weeks before the first dose of the IMP or within 5 half-lives of the drug (whichever is shorter): Strong inhibitors or inducers of CYP3A4, Strong inhibitors of CYP2D6, Strong inhibitors of P-gp and BCRP.
12. Have prior treatment with DLL3 ADC or prior treatment with a topoisomerase I inhibitor including an ADC with a topoisomerase I inhibitor payload.
13. Have received > 30 Gy of chest radiotherapy within 12 weeks prior to the first dose of the IMP, > 30 Gy of nonchest radiotherapy within 4 weeks prior to the first dose (subjects who have completed radiotherapy for brain metastases within 14 days prior to the first dose can be enrolled and palliative radiotherapy for other sites of ≤ 30 Gy is allowed if completed more than 14 days prior to the first dose).
14. Have undergone major surgery (excluding aspiration or core biopsy) or experienced significant trauma within 4 weeks prior to the first dose.
15. Female subjects who are pregnant, lactating, or planning to become pregnant during the study period to 8 months after the last dose of the IMP.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1 Dose Escalation	IDE849	Successive cohorts of participants will be treated with increasing doses of IDE849 until the maximum tolerated dose is determined.
Part 2 Dose Optimization/Expansion	IDE849	Chosen doses of IDE849 will be tested in additional participants for dose optimization and expansion.

Primary Outcome Measures

Name	Time	Method
Part 1: Safety and Tolerability of IDE849	Approximately 4 years	Incidence of dose-limiting toxicity; incidence and severity of AEs as measured by CTCAE V5.0
Part 2: Safety and Tolerability of IDE849	Approximately 4 years	Incidence of dose-limiting toxicity; incidence and severity of AEs as measured by CTCAE V5.0
Part 2: Objective Response Rate (ORR) and Investigator Assessment of IDE849	Approximately 4 years	ORR per RECIST 1.1
Part 2: Duration of Response (DOR) and Investigator Assessment of IDE849	Approximately 4 years	DOR per RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Part 1: Objective Response Rate (ORR) and Investigator Assessment of IDE849	Approximately 4 years	ORR per RECIST 1.1
Part 1: Duration of Response (DOR) and Investigator Assessment of IDE849	Approximately 4 years	DOR per RECIST 1.1
Disease Control Rate and Investigator Assessment of IDE849	Approximately 4 years	DCR per RECIST 1.1
Dose exposure response of IDE849	Approximately 4 years	Dose-exposure-response of IDE849 as measured by concentration of IDE849 in plasma

Trial Locations

Locations (9)

Sarah Cannon Research Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

The Cancer and Hematology Centers; 🇺🇸 Grand Rapids, Michigan, United States

Columbia University Medical Center - Herbert Irving Pavilion; 🇺🇸 New York, New York, United States

Sidney Kimmel Cancer Center at Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute - Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

MD Anderson; 🇺🇸 Houston, Texas, United States

Next Oncology Dallas; 🇺🇸 Irving, Texas, United States

NEXT Oncology Virginia; 🇺🇸 Fairfax, Virginia, United States

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States