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

January 21, 2026 updated by: IDEAYA Biosciences

A Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of IDE849 in Patients With DLL3-Expressing Tumors Including Small Cell Lung Cancer

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This multicenter, open-label, Phase 1/2 study is designed to further characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary anti-tumor activity of IDE849, an anti-DLL3 antibody-drug conjugate, alone and in combination with durvalumab or IDE161, in subjects with DLL3-expressing tumors including small-cell lung cancer (SCLC), high-grade neuroendocrine carcinomas (NEC), and other DLL3-positive solid tumors.

Part 1 (Dose Escalation):

Part 1A will evaluate IDE849 monotherapy, and Part 1B will evaluate IDE849 in combination with durvalumab or IDE161. This phase is designed to assess safety and tolerability, identify dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE), in subjects with extensive-stage SCLC, high-grade NEC, or other DLL3-expressing tumors.

Part 2 (Dose Expansion):

Part 2 further will evaluate IDE849 alone or in combination at selected dose levels to characterize safety, PK, immunogenicity, and preliminary anti-tumor activity in defined cohorts of subjects with extensive-stage SCLC, high-grade NEC, or other DLL3-expressing tumors.

Study Type

Interventional

Enrollment (Estimated)

208

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Not yet recruiting
        • Chris O'Brien Lifehouse
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
        • Not yet recruiting
        • Princess Alexandra Hospital
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Not yet recruiting
        • Flinders Private Hospital - Southern Oncology Clinical Research Unit (SOCRU)
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Not yet recruiting
        • Cabrini Hospital - Malvern
  • Brazil
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Not yet recruiting
        • Hospital de Cancer de Barretos - Fundacao Pio XII
      • Porto Alegre, São Paulo, Brazil, 90570-020
        • Not yet recruiting
        • Hospital de Clinicas de Porto Alegre
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Not yet recruiting
        • Faculdade de Medicina de Sao Jose do Rio Preto-SP - Hospital de Base
      • São Paulo, São Paulo, Brazil, 04543-000
        • Not yet recruiting
        • Next Brasil (Rede D'Or)
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Not yet recruiting
        • University Health Network (UHN) - Princess Margaret Cancer Centre (Princess Margaret Hospital)
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Not yet recruiting
        • McGill University Health Centre
  • Japan
    • Tokyo-To
      • Bunkyō City, Tokyo-To, Japan, 113-8677
        • Not yet recruiting
        • Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
  • South Korea
    • Gyeonggi-do
      • Gyeonggi-do, Gyeonggi-do, South Korea, 10408
        • Not yet recruiting
        • National Cancer Center
    • North Chungcheong
      • Cheongju-si, North Chungcheong, South Korea, 361-711
        • Not yet recruiting
        • Chungbuk National University Hospital
    • Seoul
      • Seoul, Seoul, South Korea, 06351
        • Not yet recruiting
        • Samsung Medical Center
      • Seoul, Seoul, South Korea, 120-749
        • Not yet recruiting
        • Severance Hospital - Yonsei Cancer Center
  • Spain
    • Madrid
      • Madrid, Madrid, Spain, 28040
        • Not yet recruiting
        • Hospital Universitario Fundación Jiménez Díaz
        • Contact:
      • Madrid, Madrid, Spain, 28050
        • Not yet recruiting
        • South Texas Accelerated Research Therapeutics Madrid - CIOCC - Universitario Sanchinarro
        • Contact:
      • Pozuelo de Alarcón, Madrid, Spain, 28223
        • Not yet recruiting
        • NEXT Madrid -Hospital Universitario Quiron Salud Madrid
        • Contact:
    • Sevilla
      • Seville, Sevilla, Spain, 41009
  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Not yet recruiting
        • Mayo Clinic Hospital - Florida
      • Orlando, Florida, United States, 32827
        • Not yet recruiting
        • Sarah Cannon Research Institute at Florida Cancer Specialists
    • Georgia
      • Atlanta, Georgia, United States, 30318
        • Not yet recruiting
        • Piedmont Physicians Medical Oncology - Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Not yet recruiting
        • The University of Chicago Medical Center - Duchossois Center for Advanced Medicine
      • Peoria, Illinois, United States, 61637
        • Not yet recruiting
        • OSF Healthcare Cancer Institute
    • Indiana
      • Fort Wayne, Indiana, United States, 46825-1623
        • Not yet recruiting
        • Fort Wayne Medical Oncology and Hematology, Inc. - Fort Wayne North Office
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Not yet recruiting
        • Dana-Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Not yet recruiting
        • Trinity Health-IHA Medical Group - Hematology Oncology - Ann Arbor Campus
      • Grand Rapids, Michigan, United States, 49546
    • New York
      • New York, New York, United States, 10032
      • New York, New York, United States, 10065
        • Not yet recruiting
        • Weill Cornell Medicine - Cutaneous Oncology and Melanoma Program
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Sidney Kimmel Cancer Center at Thomas Jefferson University
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute - Oncology Partners
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030-4000
        • Not yet recruiting
        • The University of Texas MD Anderson Cancer Center Houston, Texas 77030-4000
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • Oncology Consultants, PA - Houston
      • Irving, Texas, United States, 75039
    • Virginia
      • Fairfax, Virginia, United States, 22031
    • Washington
      • Seattle, Washington, United States, 98104
      • Seattle, Washington, United States, 98109-1023
        • Not yet recruiting
        • Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 extensive-stage SCLC neuroendocrine carcinoma (NEC), and other DLL3+ 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 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 from signing of consent through 8 months after the last dose of IDE849; men with partners of child-bearing potential must use effective contraception through 5 months after the last dose.

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 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.
  4. Have uncontrolled tumor-associated pain.
  5. Have severe cardiovascular and cerebrovascular disease
  6. Have history of clinically significant bleeding within 3 months before the first study dose.
  7. 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.
  8. Have history of immunodeficiency, with a positive human immunodeficiency virus (HIV) test.
  9. Subjects with known or suspected viral hepatitis.
  10. Have a history of active tuberculosis within 1 year before enrollment.
  11. For participants enrolling to receive the combination with durvalumab, must not 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
  12. For participants enrolling to receive the combination with IDE161, must not have had prior gastrectomy 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
  13. Have received chemotherapy within 3 weeks of first dose of IMP; immunotherapy or biologic targeted anti-tumor 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 first dose of IMP

  14. Administration of any of the following:

    • Strong inhibitors or inducers of CYP3A4
    • Strong inhibitors of CYP2D6
    • Strong inhibitors of P-gp or BCRP
    • Use of drugs with a known risk of QT prolongation

  15. For participants enrolling to receive the combination with IDE161:

    • Use of drugs of narrow therapeutic index that are sensitive substrates of MATE2-K, BCRP, and P-gp
    • Use of known moderate and strong CYP3A4/5 inducers and inhibitors is not permitted
    • Administration of PPIs
    • Use of an H2 blocking agent
    • Use of a local antacid
    • Use of drugs with a known risk of QT prolongation
  16. Have prior treatment with DLL3 ADC or prior treatment with a topoisomerase I inhibitor including an ADC with a topoisomerase I inhibitor payload.
  17. For participants enrolling to receive the combination with durvalumab, have history of prior intolerance to PD-1/PD-L1 inhibitors
  18. Have received > 30 Gy of chest radiotherapy within 12 weeks prior to the first dose of the IMP, > 30 Gy of non-chest 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).
  19. Have undergone major surgery or experienced significant trauma within 4 weeks prior to the first dose.
  20. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: Part 1A IDE849 Monotherapy (Dose Escalation)
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
IV administration
Experimental: Experimental: Part 1B IDE849 + durvalumab (Dose Escalation)
Multiple doses of IDE849 will be tested in combination with durvalumab to identify the optimal combination dose.
Drug: IDE849
IV administration
Drug: durvalumab
IV administration
Other Names:
  • durvalumab Injection [Imfinzi]
Experimental: Experimental: Part 1B IDE849 + IDE161 (Dose Escalation)
Multiple doses of IDE849 will be tested in combination with IDE161 to identify the optimal combination dose.
Drug: IDE849
IV administration
Drug: IDE161
oral administration
Experimental: Experimental: Part 2 IDE849 Monotherapy (Dose Expansion)
Chosen monotherapy doses of IDE849 will be tested in additional participants.
Drug: IDE849
IV administration
Experimental: Experimental: Part 2 IDE849 + durvalumab (Dose Expansion)
Chose combination dose of IDE849 + durvalumab will be tested in additional participants.
Drug: IDE849
IV administration
Drug: durvalumab
IV administration
Other Names:
  • durvalumab Injection [Imfinzi]
Experimental: Experimental: Part 2 IDE849 + IDE161 (Dose Expansion)
Chose combination dose of IDE849 + IDE161 will be testing in additional participants
Drug: IDE849
IV administration
Drug: IDE161
oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1A: Safety and Tolerability of IDE849 (Monotherapy)
Time Frame: approximately 4 years total study duration
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
Time Frame: approximately 4 years total study duration
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)
Time Frame: approximately 4 years total study duration
Incidence and severity and relationship of AEs and SAEs as measured by CTCAE V5.0
approximately 4 years total study duration
4. Part 2: Safety and Tolerability of IDE849 in Combination with durvalumab or IDE161 (Dose Expansion)
Time Frame: approximately 4 years total study duration
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
Time Frame: approximately 4 years total study duration
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
Time Frame: approximately 4 years total study duration
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1 and Part 2: Disease Control Rate (DCR) and Investigator Assessment of IDE849 DCR per RECIST 1.
Time Frame: approximately 4 years total study duration
approximately 4 years total study duration
Part 2: Progression-Free Survival (PFS) PFS per RECIST1.1 PFS per RECIST1.1.
Time Frame: approximately 4 years total study duration
approximately 4 years total study duration
Part 2: Overall Survival (OS)
Time Frame: approximately 4 years total study duration
Overall Survival (OS) defined as the time from first dose of IDE849 to death due to any cause
approximately 4 years total study duration
Part 1 and Part 2: Pharmacokinetics (PK) of IDE849 and in combination with durvalumab and IDE161 Blood concentrations and PK parameters.
Time Frame: approximately 4 years total study duration
approximately 4 years total study duration
6. Part 1 and Part 2: Dose-Exposure Response of IDE849 and in combination with durvalumab and IDE161 Relationship between IDE849 dose level and systemic exposure based on plasma concentration data and pharmacokinetic parameters
Time Frame: approximately 4 years total study duration
approximately 4 years total study duration
Part 1 and Part 2: Dose-Exposure Response of IDE849 and in combination with durvalumab and IDE161 Relationship between IDE849 dose level and systemic exposure based on plasma concentration data and pharmacokinetic parameters
Time Frame: approximately 4 years total study duration
approximately 4 years total study duration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IDEAYA Biosciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 14, 2025

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

September 11, 2025

First Submitted That Met QC Criteria

September 11, 2025

First Posted (Actual)

September 16, 2025

Study Record Updates

Last Update Posted (Actual)

January 23, 2026

Last Update Submitted That Met QC Criteria

January 21, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDE849-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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