A Phase 1/2 Study to Evaluate MEDI4736

MedImmune

Status and phase: Completed; Phase 2; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: MEDI4736

Study type: Interventional

Funder types: Industry

Identifiers

NCT01693562

CD-ON-MEDI4736-1108

Details and patient eligibility

About

This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in participants with advanced solid tumors followed by an expansion phase in participants with advanced solid tumors. An exploration cohort has been added to determine the safety using every 4 weeks (Q4W) dosing.

Full description

A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death ligand-1 (PD-L1)) will evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity (IM), and antitumor activity of MEDI4736 in adult participants with solid tumors. A dose exploration cohort will look at the safety profile of Q4W dosing of MEDI4736.

Enrollment: 1,022 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18 or older.
• In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.
• In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, participants must have failed, be intolerant to, be ineligible for, or have refused
• Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
• Adequate organ and marrow function.
• Participants must have at least 1 measurable lesion.
• Available archived tumor tissue sample.
• Willingness to provide consent for biopsy sample (dose-expansion only)

Exclusion criteria

• Any prior Grade ≥ 3 immune-mediated adverse event (imAE) while receiving immunotherapy
• Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
• Prior treatment with immunotherapy agents including, but not limited to, tumor necrosis factor receptor superfamily agonists or checkpoint inhibitors or natural killer (NK) cell inhibitors.
• Active or prior documented autoimmune disease within the past 2 years
• History of primary immunodeficiency
• History of organ transplant that requires use of immunosuppressives
• Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment
• Other invasive malignancy within 2 years
• Women who are pregnant or lactating
• Uncontrolled intercurrent illness
• Known history of tuberculosis
• Known to be human immunodeficiency virus (HIV) positive
• Known to be Hepatitis B or C positive (except HCC participants)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1,022 participants in 23 patient groups

Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)

Experimental group

Description:

Participants will receive intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)

Experimental group

Description:

Participants will receive IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Escalation Cohort (MEDI4736 1 mg/kg Q2W)

Experimental group

Description:

Participants will receive IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Escalation Cohort (MEDI4736 3 mg/kg Q2W)

Experimental group

Description:

Participants will receive IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Escalation Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Escalation Cohort (MEDI4736 15 mg/kg Q3W)

Experimental group

Description:

Participants will receive IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Exploration Durvalumab 20 mg/kg (Q4W)

Experimental group

Description:

Participants will receive IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion Non-SCCHN Cohort HPV positive (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with non-small-cell lung cancer (NSCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with hepatocellular carcinoma (HCC Total) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with advance cutaneous melanoma (ACM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with uveal melanoma (UM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with gastroesophageal cancer (GEC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with triple-negative breast cancer (TNBC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with pancreatic adenocarcinoma (PAC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with urothelial carcinoma (UC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with glioblastoma multiforme (GBM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with ovarian cancer (OC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with soft- tissue sarcoma (STS) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with small-cell lung cancer (SCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with microsatellite instability (MSI)-high cancer will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736

Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)

Experimental group

Description:

Participants with nasopharyngeal carcinoma (NPC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: MEDI4736