A Study of IDE849 in Patients With DLL3 Expressing Tumors Including Small Cell Lung Cancer
Purpose
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.
Conditions
- Small-cell Lung Cancer
- Neuroendocrine Carcinomas
- Solid Tumor Show to Express DLL3
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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 Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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 |
|
|
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. |
|
|
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. |
|
|
Experimental Experimental: Part 2 IDE849 Monotherapy (Dose Expansion) |
Chosen monotherapy doses of IDE849 will be tested in additional participants. |
|
|
Experimental Experimental: Part 2 IDE849 + durvalumab (Dose Expansion) |
Chose combination dose of IDE849 + durvalumab will be tested in additional participants. |
|
|
Experimental Experimental: Part 2 IDE849 + IDE161 (Dose Expansion) |
Chose combination dose of IDE849 + IDE161 will be testing in additional participants |
|
Recruiting Locations
Sarah Cannon Research Institute at HealthONE
Denver 5419384, Colorado 5417618 80218
Denver 5419384, Colorado 5417618 80218
The Cancer and Hematology Centers
Grand Rapids 4994358, Michigan 5001836 49546
Grand Rapids 4994358, Michigan 5001836 49546
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia 4560349, Pennsylvania 6254927 19107
Philadelphia 4560349, Pennsylvania 6254927 19107
Sarah Cannon Research Institute - Oncology Partners
Nashville 4644585, Tennessee 4662168 37203
Nashville 4644585, Tennessee 4662168 37203
Next Oncology Dallas
Irving 4700168, Texas 4736286 75039
Irving 4700168, Texas 4736286 75039
NEXT Oncology Virginia
Fairfax 4758023, Virginia 6254928 22031
Fairfax 4758023, Virginia 6254928 22031
More Details
- Status
- Recruiting
- Sponsor
- IDEAYA Biosciences
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.