Ignite Creation Date:
2025-12-24 @ 7:32 PM
Ignite Modification Date:
2026-01-01 @ 8:47 AM
Study NCT ID:
NCT02643303
Status:
COMPLETED
Last Update Posted:
2022-12-02
First Post:
2015-12-18
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers
Sponsor:
Ludwig Institute for Cancer Research
Organization:
Study Overview
Official Title:
A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab (MEDI4736) Plus the Toll-like Receptor Agonist Poly-ICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers
Status:
COMPLETED
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is an open-label, multicenter, Phase 1/2 study of the CTLA-4 antibody, tremelimumab, and the PD-L1 antibody, durvalumab (MEDI4736), in combination with the tumor microenvironment (TME) modulator poly-ICLC, a TLR3 agonist, in subjects with advanced, measurable, biopsy-accessible cancers.
Detailed Description:
This is an open-label, multicenter, Phase 1/2 study of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, tremelimumab, and the programmed cell death ligand-1 (PD-L1) antibody, durvalumab (MEDI4736), in combination with the tumor microenvironment (TME) modulator poly-ICLC, a toll-like receptor 3 (TLR3) agonist, in subjects with advanced, measurable, biopsy-accessible cancers. Subjects will receive intratumoral and intramuscular (IM) administration of poly-ICLC and intravenous (IV) administration of durvalumab, together with either IV or intratumoral administration of tremelimumab. The study will be conducted in 2 phases.
Phase 1: There will be enrollment to 3 subject cohorts in Phase 1, with staggered initiation of enrollment.
* Cohort 1A: IV Durvalumab + Intratumoral/IM Poly-ICLC. After safety is demonstrated in the first 3-6 subjects in Cohort 1A, Cohorts 1B and 1C will open to enrollment.
* Cohort 1B: IV Durvalumab + IV Tremelimumab + Intratumoral/IM Poly-ICLC.
* Cohort 1C: IV Durvalumab + Intratumoral Tremelimumab + Intratumoral/IM Poly-ICLC.
Phase 2: Upon determination of the recommended combination dose in Cohort 1C, up to 66 evaluable subjects will be treated in Phase 2. Up to 6 subjects will be initially enrolled by tumor type (head and neck squamous cell carcinoma, locally recurrent or metastatic breast cancer, sarcoma, Merkel cell carcinoma, cutaneous T-cell lymphoma, melanoma after failure of available therapies, genitourinary cancers and solid tumors with accessible metastases). Subjects enrolled in Cohort 1C will be included in Phase 2 in the applicable tumor type. Data from all subjects in each Phase 2 tumor type will be reviewed for safety/efficacy to select up to 3 tumor types that demonstrate an efficacy signal, defined as at least 1 of 6 subjects within a tumor type who achieve a partial response (PR) or complete response (CR) by immune-related RECIST (irRECIST) or RECIST 1.1, or stable disease (SD) for at least 6 months. Up to 6 additional subjects in each of the selected tumor types may be enrolled in the expansion.
Phase 1: There will be enrollment to 3 subject cohorts in Phase 1, with staggered initiation of enrollment.
* Cohort 1A: IV Durvalumab + Intratumoral/IM Poly-ICLC. After safety is demonstrated in the first 3-6 subjects in Cohort 1A, Cohorts 1B and 1C will open to enrollment.
* Cohort 1B: IV Durvalumab + IV Tremelimumab + Intratumoral/IM Poly-ICLC.
* Cohort 1C: IV Durvalumab + Intratumoral Tremelimumab + Intratumoral/IM Poly-ICLC.
Phase 2: Upon determination of the recommended combination dose in Cohort 1C, up to 66 evaluable subjects will be treated in Phase 2. Up to 6 subjects will be initially enrolled by tumor type (head and neck squamous cell carcinoma, locally recurrent or metastatic breast cancer, sarcoma, Merkel cell carcinoma, cutaneous T-cell lymphoma, melanoma after failure of available therapies, genitourinary cancers and solid tumors with accessible metastases). Subjects enrolled in Cohort 1C will be included in Phase 2 in the applicable tumor type. Data from all subjects in each Phase 2 tumor type will be reviewed for safety/efficacy to select up to 3 tumor types that demonstrate an efficacy signal, defined as at least 1 of 6 subjects within a tumor type who achieve a partial response (PR) or complete response (CR) by immune-related RECIST (irRECIST) or RECIST 1.1, or stable disease (SD) for at least 6 months. Up to 6 additional subjects in each of the selected tumor types may be enrolled in the expansion.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: