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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
208
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.
Time frame: 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.
Time frame: 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
Time frame: approximately 4 years total study duration
4. Part 2: Safety and Tolerability of IDE849 in Combination with durvalumab or IDE161 (Dose Expansion)
Incidence and severity and relationship of AEs and SAEs graded as measured by CTCAE V 5.0.
Time frame: 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.
Time frame: 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.
Time frame: approximately 4 years total study duration
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Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
RECRUITINGMayo Clinic Hospital - Florida
Jacksonville, Florida, United States
NOT_YET_RECRUITINGSarah Cannon Research Institute at Florida Cancer Specialists
Orlando, Florida, United States
NOT_YET_RECRUITINGPiedmont Physicians Medical Oncology - Atlanta
Atlanta, Georgia, United States
NOT_YET_RECRUITINGThe University of Chicago Medical Center - Duchossois Center for Advanced Medicine
Chicago, Illinois, United States
NOT_YET_RECRUITINGOSF HealthCare Cancer Institute
Peoria, Illinois, United States
NOT_YET_RECRUITINGFort Wayne Medical Oncology and Hematology, Inc. - Fort Wayne North Office
Fort Wayne, Indiana, United States
NOT_YET_RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
NOT_YET_RECRUITINGTrinity Health-IHA Medical Group - Hematology Oncology - Ann Arbor Campus
Ann Arbor, Michigan, United States
NOT_YET_RECRUITINGThe Cancer and Hematology Centers
Grand Rapids, Michigan, United States
RECRUITING...and 29 more locations
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
Part 2: Progression-Free Survival (PFS) PFS per RECIST1.1 PFS per RECIST1.1.
Time frame: approximately 4 years total study duration
Part 2: Overall Survival (OS)
Overall Survival (OS) defined as the time from first dose of IDE849 to death due to any cause
Time frame: 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
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
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