Description:
This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study
to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and
immunogenicity of Durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in Adult
Subjects with selected advanced solid tumors and the combination of durvalumab and
monalizumab (IPH2201) standard of care systemic therapy with or without biological agent and
monalizumab (IPH2201) with biological agent administered to subjects with recurrent or
metastatic colorectal cancer (CRC).
Title
- Brief Title: A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors
- Official Title: A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
D419NC00001
- SECONDARY ID:
D419NC00001
- NCT ID:
NCT02671435
Conditions
Purpose
This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study
to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and
immunogenicity of Durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in Adult
Subjects with selected advanced solid tumors and the combination of durvalumab and
monalizumab (IPH2201) standard of care systemic therapy with or without biological agent and
monalizumab (IPH2201) with biological agent administered to subjects with recurrent or
metastatic colorectal cancer (CRC).
Detailed Description
The study consists of 3 parts: dose escalation (Part 1), dose expansion (Part 2), and dose
exploration (Part 3). Part 1 will evaluate dose escalation of durvalumab in combination with
monalizumab in adult subjects with select advanced solid tumor malignancies. Part 2 will
evaluate further the identified dose of durvalumab in combination with monalizumab from Part
1 in adult subjects with select advanced solid tumor malignancies. Part 3 will evaluate dose
exploration of durvalumab in combination with monalizumab and standard of care systemic
therapy with or without biological agent, and monalizumab in combination with biological
agent in adult subjects with CRC.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1 -Dose escalation with 5 dose escalation cohorts | Experimental | Durvalumab and monalizumab | |
| Part 2 - Dose expansion with 4 dose expansion cohorts | Experimental | Durvalumab with monalizumab | |
| Part 3 -Dose Exploration with 10 dose exploration cohorts. | Experimental | Durvalumab and monalizumab and standard of standard of care systemic therapy with or without a biologic agent and monalizumab in combination with biologic agent in CRC. | |
Eligibility Criteria
Inclusion Criteria:
1. Subjects must have histologic documentation of advanced recurrent or metastatic
cancer.
2. Subjects must be at the recurrent/metastatic setting, with selected advanced solid
tumors.
3. Subjects must have at least one lesion that is measurable by RECIST v1.1
4. Part 3, Dose exploration, CRC subjects can be treatment naïve but should not have
received more than two line of systemic therapy in the recurrent/metastatic setting.
Exclusion Criteria
1. Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may
be permitted upon discussion with the medical monitor.
2. Prior participation in clinical studies that include durvalumab alone or in
combination, where the study has registrational intent and the analyses for the
primary endpoint have not yet been completed
3. Receipt of any conventional or investigational anticancer therapy within 4 weeks prior
to the first dose of study treatment
4. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer
treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.
| Maximum Eligible Age: | 99 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Occurrence of Drug Limited Toxicities (DLTs) |
| Time Frame: | From Time of First dose through DLT Screening period |
| Safety Issue: | |
| Description: | To assess by the occurrence of Drug Limited Toxicities (DLTs) |
Secondary Outcome Measures
| Measure: | Expression of pre-treatment protein within the tumor microenvironment |
| Time Frame: | From time of screening through 90 days (+/- 7 days) after the last dose of study medication |
| Safety Issue: | |
| Description: | To assess biomarker predicting activity of monalizumab+durva in combo with standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent |
| Measure: | Number of subjects who develop anti-drug antibodies |
| Time Frame: | From time of first dose through 90 days (+/- 7 days) after the last dose of study medication |
| Safety Issue: | |
| Description: | To assess the immunogenicity of mona+durva with or without standard of care systemic therapy or biological agent, or monalizumab + with biological agent |
| Measure: | Durva, monalizumab, biologic agent serum peak concentration (cMax) concentration for Pharmacokinetics |
| Time Frame: | From time of first dose through 90 days (+/- 7 days) after the last dose of study medication |
| Safety Issue: | |
| Description: | To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent |
| Measure: | Durva and monalizumab serum area under the concentration-time curve (AUC) concentration for Pharmacokinetics |
| Time Frame: | From time of first dose through 90 days (+/- 7 days) after the last dose of study medication |
| Safety Issue: | |
| Description: | To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, monalizumab + with biological agent |
| Measure: | Durva and monalizumab serum clearance (CL) concentration for Pharmacokinetics |
| Time Frame: | From time of first dose through 90 days (+/- 7 days) after the last dose of study medication |
| Safety Issue: | |
| Description: | To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent |
| Measure: | Durva and monalizumab serum terminal elimination half-life (t1/2) concentration for Pharmacokinetics |
| Time Frame: | From first dose through 90 days (+/- 7 days) after the last dose of study medication |
| Safety Issue: | |
| Description: | To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent |
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | From time of first dose of study medication through 5 years |
| Safety Issue: | |
| Description: | To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | From time of first dose of study medication through 5 years |
| Safety Issue: | |
| Description: | To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent |
| Measure: | Disease Control Rate (DC) |
| Time Frame: | From time of first dose of study medication through 5 years |
| Safety Issue: | |
| Description: | To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent |
| Measure: | Overall Survival (OS) |
| Time Frame: | From time of first dose of study medication through 5 years |
| Safety Issue: | |
| Description: | To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent |
| Measure: | Duration of Response (DoR) |
| Time Frame: | From time of first dose of study medication through 5 years |
| Safety Issue: | |
| Description: | To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | MedImmune LLC |
Trial Keywords
- Colorectal, colon, CRC, solid tumors, check point inhibitors, immunotherapy, metastatic
Last Updated
July 9, 2021
