A Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of IDE849 in Patients With DLL3-Expressing Tumors Including Small Cell Lung Cancer
Study Identifier:
IDE849-001
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
N/A
Study Contact Information:
N/A
Recruiting
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Study 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.
To evaluate 3.5 mg/kg IV dose once every 3-weeks (Q3W). Next, to determine the recommended Phase 2 dose (RP2D)
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
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.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Sreenivasa Chandana
Status
Recruiting
Condition(s) Treated at Site
Small Cell Lung
Neuroendocrine
Solid Tumor