A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors

MedImmune

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: Durvalumab; Drug: Bevacizumab; Drug: Cetuximab; Drug: Monalizumab; Drug: mFOLFOX6

Study type: Interventional

Funder types: Industry

Identifiers

NCT02671435

2016-000662-38 (EudraCT Number)

D419NC00001 (Other Grant/Funding Number)

Details and patient eligibility

About

This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, pharmacokinetic (PK), pharmacodynamics, and immunogenicity of durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in adult participants 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 participants with recurrent or metastatic colorectal cancer (CRC).

Full 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 participants 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 participants 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 participants with CRC.

Enrollment: 383 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Participants must have histologic documentation of advanced recurrent or metastatic cancer.
2. Participants must be at the recurrent/metastatic setting, with selected advanced solid tumors.
3. Participants must have at least one lesion that is measurable by RECIST v1.1
4. Part 3, Dose exploration, CRC participants 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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383 participants in 15 patient groups

Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W

Experimental group

Description:

Participants will receive intravenous (IV) infusions of durvalumab 1500 mg every 4 weeks (Q4W) in combination with monalizumab 22.5 mg every 2 weeks (Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed disease progression (PD), or documentation of subject withdrawal for another reason.

Treatment:

Drug: Monalizumab

Drug: Durvalumab

Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W

Experimental group

Description:

Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 75 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Monalizumab

Drug: Durvalumab

Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W

Experimental group

Description:

Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 225 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Monalizumab

Drug: Durvalumab

Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W

Experimental group

Description:

Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Monalizumab

Drug: Durvalumab

Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W

Experimental group

Description:

Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Monalizumab

Drug: Durvalumab

Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC)

Experimental group

Description:

Participants with microsatellite-stable colorectal cancer (MSS-CRC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Monalizumab

Drug: Durvalumab

Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (ovarian)

Experimental group

Description:

Participants with ovarian cancer will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Monalizumab

Drug: Durvalumab

Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS)

Experimental group

Description:

Participants with endometrial MSS will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Monalizumab

Drug: Durvalumab

Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC)

Experimental group

Description:

Participants with non-small cell lung cancer (NSCLC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Monalizumab

Drug: Durvalumab

Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W

Experimental group

Description:

Participants with first-line (1L) MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus mFOLFOX (oxaliplatin 85 mg/m\^2 IV infusion, folinic acid 400 mg/m\^2 infusion, fluorouracil 400 mg/m\^2 IV bolus, followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of bevacizumab 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: mFOLFOX6

Drug: Monalizumab

Drug: Bevacizumab

Drug: Durvalumab

Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W

Experimental group

Description:

Participants with 1L MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 (oxaliplatin 85 mg/m\^2, folinic acid 400 mg/m\^2, fluorouracil 400 mg/m\^2 IV bolus, followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of cetuximab (loading dose of 400 mg/m\^2 on Day 1, followed by maintenance dose of 250 mg/m\^2 IV infusion every week starting on Day 8, then changed to 500 mg/m\^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: mFOLFOX6

Drug: Cetuximab

Drug: Monalizumab

Drug: Durvalumab

Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W

Experimental group

Description:

Participants with recurrent or metastatic third-line (3L) RAS mutant MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m\^2 on Day 1 then 500 mg/m\^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Cetuximab

Drug: Monalizumab

Drug: Durvalumab

Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W

Experimental group

Description:

Participants with recurrent or metastatic 3L RAS mutant MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m\^2 on Day 1 then 500 mg/m\^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Cetuximab

Drug: Monalizumab

Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W

Experimental group

Description:

Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m\^2 on Day 1 then 500 mg/m\^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Cetuximab

Drug: Monalizumab

Drug: Durvalumab

Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W

Experimental group

Description:

Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m\^2 on Day 1 then 500 mg/m\^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Treatment:

Drug: Cetuximab

Drug: Monalizumab