A Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of IDE849 in Patients With DLL3-Expressing Tumors Including Small Cell Lung Cancer
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.
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.
Arms & interventions
- DrugIDE849
IV administration
- Drugdurvalumab
IV administration
- DrugIDE161
oral administration
Outcome measures
Primary
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
Secondary
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)
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
Eligibility criteria
Study locations (20)
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
Mayo Clinic Hospital - Florida
Jacksonville, Florida, 32224
Sarah Cannon Research Institute at Florida Cancer Specialists
Orlando, Florida, 32827
Piedmont Physicians Medical Oncology - Atlanta
Atlanta, Georgia, 30318
The University of Chicago Medical Center - Duchossois Center for Advanced Medicine
Chicago, Illinois, 60637
OSF HealthCare Cancer Institute
Peoria, Illinois, 61637
Fort Wayne Medical Oncology and Hematology, Inc. - Fort Wayne North Office
Fort Wayne, Indiana, 46825-1623
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Trinity Health-IHA Medical Group - Hematology Oncology - Ann Arbor Campus
Ann Arbor, Michigan, 48106
The Cancer and Hematology Centers
Grand Rapids, Michigan, 49546
Columbia University Medical Center - Herbert Irving Pavilion
New York, New York, 10032
Weill Cornell Medicine - Cutaneous Oncology and Melanoma Program
New York, New York, 10065
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Sarah Cannon Research Institute - Oncology Partners
Nashville, Tennessee, 37203
The University of Texas MD Anderson Cancer Center Houston, Texas 77030-4000
Houston, Texas, 77030-4000
Oncology Consultants, PA - Houston
Houston, Texas, 77030
Next Oncology Dallas
Irving, Texas, 75039
NEXT Oncology Virginia
Fairfax, Virginia, 22031
Swedish Cancer Institute
Seattle, Washington, 98104
Seattle Cancer Care Alliance
Seattle, Washington, 98109-1023