A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01975831
Recruitment Status : Active, not recruiting
First Posted : November 5, 2013
Last Update Posted : March 6, 2018
MedImmune LLC
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

Brief Summary:
This is a multicenter, open-label, study with a standard 3+3 dose-escalation phase, followed by an expansion phase in subjects with solid tumors

Condition or disease Intervention/treatment Phase
Breast Cancer Ovarian Cancer Colorectal Cancer Cervical Cancer Renal Cell Carcinoma Drug: MEDI4736 Drug: Tremelimumab Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 106 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Evaluate the Safety and Tolerability of Anti-PD-L1, MEDI4736, in Combination With Tremelimumab in Subjects With Advanced Solid Tumors
Study Start Date : December 19, 2013
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: MEDI4736 & Tremelimumab Treatment
MEDI4736 and Tremelimumab will be administered by IV infusion
Drug: MEDI4736
Other Name: Durvalumab

Drug: Tremelimumab

Primary Outcome Measures :
  1. Number of adverse events [ Time Frame: Up to 1 year ]

Secondary Outcome Measures :
  1. Area under the concentration time curve, maximum concentration, clearance, half-life after administration of MEDI4736 and Tremelimumab [ Time Frame: Up to 15 months ]
  2. Number and percentage of subjects who develop detectable anti-drug antibodies (ADAs) [ Time Frame: Up to 15 months ]
  3. Tumor Response by the Immune-related Response Criteria [ Time Frame: Up to 12 months ]
  4. Tumor Response using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 12 months ]
  5. Progression-free Survival [ Time Frame: Up to 5 years ]
  6. Overall Survival [ Time Frame: Up to 5 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically- or cytologically-confirmed ovarian cancer, colorectal cancer, non-triple negative breast cancer, renal cell carcinoma and cervical cancer, with at least one lesion measurable by irRC not previously irradiated.
  2. Failed to respond to or relapsed following standard treatment, or declined or was not eligible for standard treatment.
  3. ECOG performance status of 0-2.
  4. Anticipated lifespan greater than 6 month.
  5. At the time of day 1 of the study, subjects with brain metastases must be asymptomatic for at least 4 weeks and:

    • at least 8 weeks without tumor progression after any whole brain radiotherapy
    • at least 4 weeks since craniotomy and resection or stereotactic radiosurgery
    • at least 3 weeks without new brain metastases as evidenced by MRI/CT
  6. Adequate organ and marrow function , as defined below:

    • Hemoglobin ≥ 9 g/dL
    • Absolute Neutrophil Count ≥ 1500/mm3
    • Platelet count ≥ 100,000/mm3
    • Total bilirubin within normal ranges unless associated with hepatobiliary metastases or Gilbert syndrome, then total bilirubin ≤ 2 x ULN
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN unless associated with hepatic metastases, then ALT and AST ≤ 5 x ULN
    • Creatinine ≤ 2.0 mg/dL
  7. Have been informed of other treatment options.
  8. Age ≥18 years.
  9. Able and willing to give valid written informed consent.
  10. Able and willing to give valid written consent for archival tumor samples
  11. Able and willing to give valid written consent for biopsy samples (subjects in the expansion phase only).

Exclusion Criteria:

  1. Prior exposure to tremelimumab or MEDI4736 or other anti-CTLA-4, anti-PD-1, anti-PDL1 antibodies
  2. History of severe allergic reactions to any unknown allergens or any components of the study drugs.
  3. Active or prior autoimmune disease except for autoimmune thyroiditis or vitiligo.
  4. Any prior Grade ≥ 3 immune-related adverse event (irAE) or any prior corticosteroid-refractory irAE.
  5. Known active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months.
  6. History of sarcoidosis syndrome.
  7. Active or history of inflammatory bowel disease (colitis, Crohn's), diverticulitis, irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegener's granulomatosis.
  8. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available.
  9. Known immunodeficiency or active HIV.
  10. Other active serious illnesses (e.g., serious infections requiring antibiotics).
  11. If a subject previously received investigational treatment, the last dose of investigational treatment was administered within 4 weeks of Day 1 of the study or adverse event(s) attributable to investigational treatment have not resolved to Grade 1 or better.
  12. Major surgical procedure (as defined by the investigator) within 30 days prior to Day 1 or still recovering from prior surgery.
  13. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
  14. Lack of availability for immunological and clinical follow-up assessments.
  15. Women who are breast feeding or pregnant as evidenced by positive serum pregnancy test.
  16. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of effective contraception from screening, and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.

    Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Nonsterilized males who are sexually active with a female partner of childbearing potential must use 2 acceptable methods of effective contraception from Day 1 and for 6 months after receipt of the final dose of investigational product.

  17. Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01975831

United States, California
Los Angeles, California, United States
United States, Connecticut
New Haven, Connecticut, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, New York
Research Site
Buffalo, New York, United States
Research Site
New York, New York, United States
United States, Texas
Dallas, Texas, United States
United States, Virginia
Charlottesville, Virginia, United States
Sponsors and Collaborators
Ludwig Institute for Cancer Research
MedImmune LLC
Cancer Research Institute, New York City
Study Chair: Jedd Wolchok, MD, PhD MSKCC

Responsible Party: Ludwig Institute for Cancer Research Identifier: NCT01975831     History of Changes
Other Study ID Numbers: LUD2013-003
First Posted: November 5, 2013    Key Record Dates
Last Update Posted: March 6, 2018
Last Verified: March 2018

Keywords provided by Ludwig Institute for Cancer Research:
Non Triple Negative Breast Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Uterine Cervical Neoplasms
Carcinoma, Renal Cell
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Kidney Diseases
Urologic Diseases
Antibodies, Monoclonal
Immunologic Factors