
A Phase 1/2 Study to Evaluate MEDI4736
Study Purpose
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.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years - 99 Years |
Gender | All |
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.
Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT01693562 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 1/Phase 2 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
MedImmune LLC |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
MedImmune, LLC |
Principal Investigator Affiliation | MedImmune LLC |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
Overall Status | Completed |
Countries | Belgium, Canada, France, Germany, Italy, Korea, Republic of, Taiwan, United Kingdom, United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Advanced Solid Tumors |
Study Website: | View Trial Website |
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.
Arms
Experimental: Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)
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.
Experimental: Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)
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.
Experimental: Escalation Cohort (MEDI4736 1 mg/kg Q2W)
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.
Experimental: Escalation Cohort (MEDI4736 3 mg/kg Q2W)
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.
Experimental: Escalation Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Escalation Cohort (MEDI4736 15 mg/kg Q3W)
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.
Experimental: Exploration Durvalumab 20 mg/kg (Q4W)
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.
Experimental: Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion Non-SCCHN Cohort HPV positive (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)
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.
Experimental: Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
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.
Interventions
Drug: - MEDI4736
Participants will receive IV infusion of MEDI4736 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.
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
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Scottsdale, Arizona, 85258
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Burbank, California, 91505
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Gilroy, California, 95020
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Los Angeles, California, 90025
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Los Angeles, California, 90095
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Orange, California, 92868
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Palo Alto, California, 94304-5826
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San Francisco, California, 94115
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Whittier, California, 90603
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New Haven, Connecticut, 06520
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Washington, District of Columbia, 20007
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Jacksonville, Florida, 32224
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Miami Beach, Florida, 33140
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Tampa, Florida, 33612
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Athens, Georgia, 30607
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Augusta, Georgia, 30912
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Chicago, Illinois, 60637
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Baltimore, Maryland, 21201
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Baltimore, Maryland, 21231
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Boston, Massachusetts, 02215
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Ann Arbor, Michigan, 48109
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Detroit, Michigan, 48201
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Minneapolis, Minnesota, 55407
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Saint Louis Park, Minnesota, 55416
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Billings, Montana, 59101
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Las Vegas, Nevada, 89169
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Hackensack, New Jersey, 07601
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Paterson, New Jersey, 07503
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Bronx, New York, 10461
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New York, New York, 10065
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Chapel Hill, North Carolina, 27599
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Huntersville, North Carolina, 28078
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Cleveland, Ohio, 44106
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Columbus, Ohio, 43210
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Portland, Oregon, 97213
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Philadelphia, Pennsylvania, 19107-5097
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Pittsburgh, Pennsylvania, 15212
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Greenville, South Carolina, 29605
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Nashville, Tennessee, 37203
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Dallas, Texas, 75201
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Houston, Texas, 77030
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Houston, Texas, 77090
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San Antonio, Texas, 78229
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Salt Lake City, Utah, 84403
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Blacksburg, Virginia, 24060
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Fairfax, Virginia, 22031
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Seattle, Washington, 98104
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Gent, , 9000
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Leuven, , 3000
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Namur, , 5000
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Ottawa, Ontario, K1H 8L6
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Toronto, Ontario, M5G 2M9
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Montreal, Quebec, H2X 3E4
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Paris Cedex 10, , 75475
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Heidelberg, , 69120
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Milano, , 20132
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Milan, , 20141
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Napoli, , 80131
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Siena, , 53100
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Gwangju, , 61469
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Seo-Gu, , 49241
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Seongnam-si, , 13620
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Seoul, , 03080
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Seoul, , 05505
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Seoul, , 06351
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Tainan, , 70403
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Taipei, , 10002
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London, , EC1A 7BE
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London, , SW2 6JJ
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