NCT02643303

A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers

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
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 58 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Head and Neck Squamous Cell Carcinoma
• Breast Cancer
• Sarcoma
• Merkel Cell Carcinoma
• Cutaneous T-Cell Lymphoma
• Melanoma
• Renal Cancer
• Bladder Cancer
• Prostate Cancer
• Testicular Cancer
• Solid Tumor

Interventions

Type	Name	Description
DRUG	Durvalumab
DRUG	Tremelimumab
DRUG	Poly-ICLC

Timeline

• Start date: 2016-12-28
• Primary completion: 2022-02-23
• Completion: 2022-02-23
• First posted: 2015-12-31
• Last updated: 2022-12-02
• Results posted: 2022-12-02

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study