A Phase 1/2 Study to Evaluate MEDI4736

NCTId: NCT01693562

Official Title

A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI4736 in Subjects With Advanced Solid Tumors

Summary

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

Detailed Description

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

Eligibility

Eligibility Criteria

Gender Minimum Age Maximum Age Healthy Volunteers?
Both 18 Years N/A False

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, subjects must have failed, be intolerant to, be ineligible for, or have refused treatment.

- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.

- Adequate organ and marrow function.

- Subjects must have at least 1 measurable lesion.

- Available archived tumor tissue sample.

- Willingness to provide consent for biopsy samples (dose-expansion only)

Exclusion Criteria:

- Any prior Grade ≥ 3 irAE 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.

- 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 (excpet HCC patients)

Interventions & Outcomes

Study Interventions & Types

Drug Intervention(s)

MEDI4736 - MEDI4736 will be administered by IV infusion every 14 or 21 days.
MEDI4736 - MEDI4736 will be administered by IV infusion every 14, 21, or 28 days.

Study Outcomes

Primary Outcome(s)

Timeframe: Until end of study
Measure: Anti-tumor efficacy (dose expansion subjects)
Description: Evaluate the objective response rate in subjects with non-squamous NSCLC who have received 2 or more prior lines of therapy and subjects with squamous NSCLC who have received 1 prior lines of therapy and 2 or more prior lines of therapy
Safety Issue? No

Timeframe: 90 days after the last dose of MEDI4736
Measure: Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs).
Description: MTD or OBD will be determined by the number of participants experiencing dose-limiting toxicities. Safety profile will be assessed through number of participants experiencing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, and physical examinations.
Safety Issue? Yes

Secondary Outcome(s)

Measure: Area under the concentration time curve, maximum concentration, clearance, half-life after administration of MEDI4736.
Timeframe: Up to 90 days after the last dose of MEDI4736
Description: If data allow, noncompartmental PK parameters (AUC, Cmax, CL, t½) will be estimated.
Safety Issue? No

Measure: Disease control rate (DCR)
Timeframe: Until end of study
Description: The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥ 12 weeks)
Safety Issue? No

Measure: Duration of response (DR)
Timeframe: Until end of study
Description: Duration of response will be defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
Safety Issue? No

Measure: Number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Timeframe: Up to 6 months after the last dose of MEDI4736.
Description: The immunogenic potential of MEDI4736 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Safety Issue? Yes

Measure: Objective response rate (ORR)
Timeframe: Until end of study
Description: The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR
Safety Issue? No

Measure: Overall survival (OS)
Timeframe: From first dose of study drug until death or up to 2 years
Description: Overall survival will be determined as the time from the start of treatment with MEDI4736 until death.
Safety Issue? No

Measure: Progression-free survival (PFS)
Timeframe: Until end of study
Description: Progression-free survival is the time interval from the start of treatment with MEDI4736 until the documentation of confirmed immune-related disease progression or death due to any cause, whichever occurs first.
Safety Issue? No

Facility Locations

Research Study Facility Map

Map of facility locations for this research study.

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Clinical Research Study Facility Locations

Recruiting

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Nashville, Tennessee United States

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Dallas, Texas United States

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Houston, Texas United States

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San Antonio, Texas United States

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Salt Lake City, Utah United States

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Leuven, Belgium

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Liege, Belgium

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Toronto, Ontario Canada

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Montreal, Quebec Canada

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Paris Cedex 10, France

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Villejuif Cedex, France

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Berlin, Germany

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Gauting, Germany

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Heidelberg, Germany

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Milano, Italy

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Napoli, Italy

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Siena, Italy

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Seoul, Korea, Republic of

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London, United Kingdom

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Northwood, United Kingdom

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Oxford, United Kingdom

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Sutton, United Kingdom

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Philadelphia, Pennsylvania United States

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Portland, Oregon United States

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Columbus, Ohio United States

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Cleveland, Ohio United States

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Huntersville, North Carolina United States

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Chapel Hill, North Carolina United States

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New York, New York United States

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Hackensack, New Jersey United States

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Billings, Montana United States

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Minneapolis, Minnesota United States

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Detroit, Michigan United States

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Ann Arbor, Michigan United States

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Baltimore, Maryland United States

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Chicago, Illinois United States

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Augusta, Georgia United States

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Tampa, Florida United States

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Miami Beach, Florida United States

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Washington, District of Columbia United States

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New Haven, Connecticut United States

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Stanford, California United States

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Orange, California United States

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Los Angeles, California United States

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Gilroy, California United States

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Scottsdale, Arizona United States

Related Keywords & Studies

Conditions and Diseases with Related Research Studies

  1. Advanced Malignant Melanoma
  2. Renal Cell Carcinoma
  3. Non-Small Cell Lung Cancer
  4. Colorectal Cancer
  5. Advanced Solid Tumors

Other Related Condition Keywords

  1. Carcinoma
  2. Carcinoma, Non-Small-Cell Lung
  3. Carcinoma, Renal Cell
  4. Colorectal Neoplasms
  5. Lung Neoplasms
  6. Melanoma
  7. Neoplasms