A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Ludwig Institute for Cancer Research
MedImmune LLC
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
First received: October 29, 2013
Last updated: November 25, 2015
Last verified: November 2015
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 Intervention Phase
Breast Cancer
Ovarian Cancer
Colorectal Cancer
Cervical Cancer
Renal Cell Carcinoma
Drug: MEDI4736
Drug: Tremelimumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:
  • Number of adverse events [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Area under the concentration time curve, maximum concentration, clearance, half-life after administration of MEDI4736 and Tremelimumab [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
  • Number and percentage of subjects who develop detectable anti-drug antibodies (ADAs) [ Time Frame: Up to 15 months ] [ Designated as safety issue: Yes ]
  • Tumor Response by the Immune-related Response Criteria [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Tumor Response using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Progression-free Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 105
Study Start Date: December 2013
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI4736 & Tremelimumab Treatment
MEDI4736 and Tremelimumab will be administered by IV infusion
Drug: MEDI4736
Other Name: Durvalumab
Drug: Tremelimumab


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01975831

Contact: Andrew Park, PharmD 212-450-1515 clintrialinformation@licr.org

United States, Massachusetts
Research Site Recruiting
Boston, Massachusetts, United States
United States, New York
Research Site Recruiting
Buffalo, New York, United States
Research Site Recruiting
New York, New York, 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
  More Information

Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT01975831     History of Changes
Other Study ID Numbers: LUD2013-003 
Study First Received: October 29, 2013
Last Updated: November 25, 2015
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Uterine Cervical Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Kidney Diseases
Kidney Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2016