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

NCT07174583 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IDE849-001
• Study Type: interventional
• Target: 262
• Locations: 1 country
• Sites: 13

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.

Conditions

Solid Tumor Show to Express DLL3; Small-cell Lung Cancer; Neuroendocrine Carcinomas

Keywords

IDE849; Small Cell Lung Cancer; SCLC; anti-DLL3 immunoglobulin G1 monoclonal antibody; DLL3; Neuroendocrine Carcinomas; NEC; durvalumab; IDE161

Outcome Measures

Primary Outcomes (6)

• Part 1A: Safety and Tolerability of IDE849 (Monotherapy)

  Incidence of dose-limiting toxicities, incidence and severity AEs and SAEs as measured by CTCAE V5.0.

  approximately 4 years total study duration

• Part 1B: Safety and Tolerability of IDE849 in Combination with durvalumab or IDE161

  Incidence of dose-limiting toxicities, incidence and severity AEs and SAEs as measured by CTCAE V5.0.

  approximately 4 years total study duration

• Part 2: Safety and Tolerability of IDE849 (Monotherapy Dose Expansion)

  Incidence and severity and relationship of AEs and SAEs as measured by CTCAE V5.0

  approximately 4 years total study duration

• Part 2: Safety and Tolerability of IDE849 in Combination with durvalumab or IDE161 or durvalumab + carboplatin (Dose Expansion)

  Incidence and severity and relationship of AEs and SAEs graded as measured by CTCAE V 5.0.

  approximately 4 years total study duration

• Part 2: Objective Response Rate (ORR) and Investigator Assessment of IDE849 ORR per RECIST 1.1

  ORR per RECIST v1.1, defined as the proportion of subjects with a Complete Response (CR) or Partial Response (PR) as assessed by the Investigator.

  approximately 4 years total study duration

• Part 2: Duration of Response (DOR) and Investigator Assessment of IDE849 DOR per RECIST 1.1

  DOR per RECIST v1.1, defined as the time from the first documented Complete Response (CR) or Partial Response (PR) to disease progression or death, whichever occurs first, as assessed by the Investigator.

  approximately 4 years total study duration

Secondary Outcomes (6)

• Part 1 and Part 2: Disease Control Rate (DCR) and Investigator Assessment of IDE849 DCR per RECIST 1.

  approximately 4 years total study duration

• Part 2: Progression-Free Survival (PFS) PFS per RECIST1.1 PFS per RECIST1.1.

  approximately 4 years total study duration

• Part 2: Overall Survival (OS)

  approximately 4 years total study duration

• Part 1 and Part 2: Pharmacokinetics (PK) of IDE849 and in combination with durvalumab, durvalumab + carboplatin, and IDE161 Blood concentrations and PK parameters.

  approximately 4 years total study duration

• Part 1 and Part 2: Dose-Exposure Response of IDE849 and in combination with durvalumab, durvalumab + carboplatin, and IDE161 Relationship between IDE849 dose level and systemic exposure based on plasma concentration data and pharmacokinetic parameters

  approximately 4 years total study duration

Study Arms (9)

Part 1A IDE849 Monotherapy (Dose Escalation)

EXPERIMENTAL

Successive cohorts of participants will be treated with escalating doses of IDE849 until the maximum tolerated dose and dose for expansion are determined

Drug: IDE849

Part 1B IDE849 + durvalumab, or IDE849 + durvalumab + carboplatin (Dose Escalation)

EXPERIMENTAL

Multiple doses of IDE849 will be tested in combination with durvalumab or in combination with durvalumab + carboplatin to identify the optimal combination dose.

Drug: IDE849; Drug: durvalumab; Drug: Carboplatin

Part 1B IDE849 + IDE161 (Dose Escalation)

EXPERIMENTAL

Multiple doses of IDE849 will be tested in combination with IDE161 to identify the optimal combination dose.

Drug: IDE849; Drug: IDE161

Part 2 IDE849 Monotherapy RDE 1 for SCLC (Dose Expansion)

EXPERIMENTAL

Chosen monotherapy doses of IDE849 will be tested in additional participants.

Drug: IDE849

Part 2 IDE849 Monotherapy RDE 2 for SCLC (Dose Expansion)

EXPERIMENTAL

Chosen monotherapy doses of IDE849 will be tested in additional participants

Drug: IDE849

Part 2 IDE849 Monotherapy for NEC (Dose Expansion)

EXPERIMENTAL

Chosen monotherapy doses of IDE849 will be tested in additional participants.

Drug: IDE849

Part 2 IDE849 + durvalumab (Dose Expansion)

EXPERIMENTAL

Chosen combination dose of IDE849 + durvalumab will be tested in additional participants.

Drug: IDE849; Drug: durvalumab

Part 2 IDE849 + durvalumab + carboplatin (Dose Expansion)

EXPERIMENTAL

Chosen combination dose of IDE849 + durvalumab + carboplatin will be tested in additional participants.

Drug: IDE849; Drug: durvalumab; Drug: Carboplatin

Part 2 IDE849 + IDE161 (Dose Expansion)

EXPERIMENTAL

Chosen combination dose of IDE849 + IDE161 will be testing in additional participants

Drug: IDE849; Drug: IDE161

Interventions

durvalumab DRUG

IV administration

Also known as: durvalumab Injection [Imfinzi]

Part 1B IDE849 + durvalumab, or IDE849 + durvalumab + carboplatin (Dose Escalation); Part 2 IDE849 + durvalumab (Dose Expansion); Part 2 IDE849 + durvalumab + carboplatin (Dose Expansion)

IDE161 DRUG

oral administration

Part 1B IDE849 + IDE161 (Dose Escalation); Part 2 IDE849 + IDE161 (Dose Expansion)

IDE849 DRUG

IV administration

Part 1A IDE849 Monotherapy (Dose Escalation); Part 1B IDE849 + IDE161 (Dose Escalation); Part 1B IDE849 + durvalumab, or IDE849 + durvalumab + carboplatin (Dose Escalation); Part 2 IDE849 + IDE161 (Dose Expansion); Part 2 IDE849 + durvalumab (Dose Expansion); Part 2 IDE849 + durvalumab + carboplatin (Dose Expansion); Part 2 IDE849 Monotherapy RDE 1 for SCLC (Dose Expansion); Part 2 IDE849 Monotherapy RDE 2 for SCLC (Dose Expansion); Part 2 IDE849 Monotherapy for NEC (Dose Expansion)

Carboplatin DRUG

IV administration

Part 1B IDE849 + durvalumab, or IDE849 + durvalumab + carboplatin (Dose Escalation); Part 2 IDE849 + durvalumab + carboplatin (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are willing to participate in this clinical study, understand the study procedures, and are able to sign the written ICF.
• Subjects with histologically or cytologically confirmed ES- SCLC, neuroendocrine carcinoma (NEC), DLL3+ solid tumors, are eligible per protocol. Subjects must have radiologically progressed or recurred after previous standard treatment.
• For SCLC, this includes 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, or were intolerant to immunotherapy and chemotherapy may enroll to receive monotherapy or IDE161 combination.
• Subjects with NEC, this includes
• High-grade gastroenteropancreatic NEC
• NEC of the prostate
• Small cell NEC of any other organ
• Merkel cell carcinoma
• Transformed non-small cell adenocarcinoma of the lung (including but not limited to epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene homolog mutated adenocarcinoma of the lung post progression on targeted therapies
• Any other NEC that does not meet any of the indications noted above.
• Subjects with other solid tumors demonstrated to express moderate/high expression of DLL3 including metastatic melanoma, Grade 3 gastrointestinal and pancreatic NETs, and pulmonary carcinoids.
• metastatic melanoma
• Subjects will be required to provide blood/tumor tissue samples for biomarker testing.
• Have at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.

You may not qualify if:

• Have mixed SCLC and NSCLC histology are not allowed (SCLC with components of large cell NEC are eligible). Participants with limited stage SCLC are ineligible.
• Subjects with locally untreated (radiotherapy or surgery) or active central nervous system (CNS) tumor metastasis.
• Have had other malignancies within 2 years prior to the first dose, except adequately treated carcinoma in situ (cervical, breast, or other), basal cell or squamous cell skin cancer, localized prostate cancer after curative therapy with no recurrence, or papillary thyroid cancer after curative resection; other prior or concurrent malignancies may be eligible with Medical Monitor review and approval.
• Have uncontrolled tumor-associated pain.
• Have severe cardiovascular and cerebrovascular disease
• Have history of clinically significant bleeding within 3 months before the first study dose.
• 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.
• Have history of immunodeficiency, with a positive human immunodeficiency virus (HIV) test at screening (HIV antibody positive and HIV-RNA above the lower limit of detection of the analytical method).
• Subjects with known or suspected viral hepatitis.
• Have a history of active tuberculosis within 1 year before enrollment.
• For participants enrolling to receive the combination with durvalumab, must not be deemed by the Investigator to be unsuitable to receive immunotherapy, or have had any prior intolerance to PD-1/PD-L1 inhibitor therapy, or have had any prior Grade 2 or higher myocarditis or any other Grade 3 or higher immune-related AE. If the participant has had a prior immune-related AE, must have recovered to Grade \< 1.
• For participants enrolling to receive the combination with IDE161, must not have had prior GI or upper bowel removal or any other gastrointestinal disorder or defect (eg, malabsorption disorder such as Crohn's disease or ulcerative colitis), that would interfere with absorption of IDE161.
• For patients receiving a combination with carboplatin, be deemed by the Investigator to be unsuitable to receive platinum-based chemotherapy, or have had intolerance to platinum-based chemotherapy
• Have received chemotherapy within 3 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 longer); other investigational products within 4 weeks or within 5 half-lives of the drug (whichever is longer) unless, in the opinion of the Investigator and Sponsor, the medication will not interfere with the study. Participants who received an immunotherapy agent (eg, PD-1/PD-L1 inhibitor) immediately prior to study enrollment must have documented radiologic disease progression as per the Investigator prior to the first dose of IMP
• Administration of any of the following:

Sponsors & Collaborators

• IDEAYA Biosciences: lead

Study Sites (13)

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, 32827, United States

RECRUITING

Fort Wayne Medical Oncology and Hematology, Inc. - Fort Wayne North Office

Fort Wayne, Indiana, 46825-1623, United States

RECRUITING

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

The Cancer and Hematology Centers

Grand Rapids, Michigan, 49546, United States

RECRUITING

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, 10032, United States

RECRUITING

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Sarah Cannon Research Institute - Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4000, United States

RECRUITING

Oncology Consultants, PA- Houston

Houston, Texas, 77030, United States

RECRUITING

Next Oncology Dallas

Irving, Texas, 75039, United States

RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Neuroendocrine

Interventions

durvalumab; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Central Study Contacts

IDEAYA Clinical Trials

CONTACT

+1-855-433-2246; IDEAYAClinicalTrials@ideayabio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: September 16, 2025
• Study Start: October 14, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)