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IDE849 for DLL3-expressing tumors including small-cell lung cancer

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

Phase1; Phase2 Interventional IDEAYA Biosciences · NCT07174583

This trial tests IDE849, alone and with durvalumab or IDE161, to see if it is safe and can shrink DLL3-positive tumors in people with small-cell lung cancer or other DLL3-expressing cancers.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment208 (estimated)
Ages18 Years and up
SexAll
SponsorIDEAYA Biosciences Industry-sponsored
Drugs / interventionsdurvalumab, chemotherapy, immunotherapy
Locations39 sites (Denver, Colorado and 38 other locations)
Trial IDNCT07174583 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label Phase 1/2 trial gives IDE849, an anti-DLL3 antibody–drug conjugate, alone and in combination with durvalumab or IDE161 to people with DLL3-positive tumors including extensive-stage small‑cell lung cancer and high‑grade neuroendocrine carcinomas. Part 1 uses dose escalation (monotherapy in 1A and combinations in 1B) to define safety, dose‑limiting toxicities, the maximum tolerated dose, and the recommended dose for expansion. Part 2 opens expansion cohorts at selected doses to further characterize safety, pharmacokinetics, immunogenicity, and preliminary anti‑tumor activity. The study requires measurable disease and collection of tumor or blood samples for DLL3 and other biomarker testing.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed DLL3-expressing tumors (including extensive-stage SCLC or high‑grade NEC), measurable recurrent or metastatic disease, and prior progression after standard therapies who can provide tumor or blood samples for biomarker testing.

Not a fit: Patients whose tumors do not express DLL3, who exceed the allowed number of prior therapies, or who are medically unable to tolerate investigational agents are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, IDE849 could provide a new targeted treatment option for patients with DLL3-positive tumors and potentially improve tumor responses or survival.

How similar studies have performed: Previous anti‑DLL3 antibody–drug conjugates produced early responses in some patients but failed to show clear benefit in larger trials, so the approach has biological rationale but remains unproven.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Denver, Colorado and 38 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Small-cell Lung CancerNeuroendocrine CarcinomasSolid Tumor Show to Express DLL3IDE849Small Cell Lung CancerSCLCanti-DLL3 immunoglobulin G1 monoclonal antibodyDLL3
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.