A Phase 1b Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer

NCT02000947 | Completed Phase 1 FDA Drug

• 2 other identifiers: D4190C000062015-003715-38
• Study Type: interventional
• Target: 459
• Locations: 9 countries
• Sites: 69

Brief Summary

The purpose of this study is to determine if MEDI4736 will be adequately tolerated in combination with tremelimumab in subjects with advanced non-small cell lung cancer (NSCLC).

Conditions

NSCLC; Non-small Cell Lung Cancer; Lung Cancer

Keywords

anti-CTLA-4; anti-PD-L1; immunotherapy; IMTC

Outcome Measures

Primary Outcomes (3)

• Number of subjects reporting adverse events

  The number of subjects reporting adverse events (AEs) and number (percentage) of subjects reporting serious adverse events (SAEs) as graded by CTCAE Version 4.03

  Screening through 90 days after the last dose of study medication

• Objective response

  Best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as defined as the best response among all overall responses recorded from the start of treatment until progression, or the last evaluable disease assessment in the absence of progressive disease (PD) prior to the initiation of subsequent anti-cancer therapy, or discontinuation from the study, whichever occurs first.

  At least 24 weeks as compared to baseline

• Number of subjects experiencing dose-limiting toxicities (DLTs)

  The maximum tolerated dose (MTD), which is the highest dose within a cohort where no more than 1 out of 6 subjects experience DLTs or the highest protocol-defined dose for each agent in the absence of exceeding the MTD, will be evaluated using the following safety assessments: adverse events, serious advents, laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results. Measurements will be aggregated to determine whether a subject has experienced a DLT as assessed by the investigator.

  Depending upon the cohort, the DLT evaluation period is from the 1st dose of study medication until (1) the 3rd dose of MEDI4736 and tremelimumab (2) the 2nd dose of MEDI4736 and tremelimumab or (3) the 3rd dose of MEDI4736 and 2nd dose of tremelimumab

Secondary Outcomes (4)

• Immunogenicity of tremelimumab in combination with MEDI4736

  During treatment through study completion, about 2 years

• Antitumor activity of tremelimumab in combination with MEDI4736

  During treatment through study completion, about 2 years

• Pharmacokinetic parameters

  During treatment through study completion, about 2 years

• Number of subjects reporting adverse events

  Screening through 90 days after the last dose of study medication

Other Outcomes (1)

• Biomarkers

  During treatment through study completion, about 2 years

Study Arms (4)

Dose Escalation

EXPERIMENTAL

MEDI4736 and tremelimumab received by intravenous infusion.

Drug: MEDI4736; Drug: Tremelimumab

Arm A

EXPERIMENTAL

Medi4736 and tremelimumab received by intravenous infusion

Drug: MEDI4736; Drug: Tremelimumab

Arm B

EXPERIMENTAL

MEDI4736 and tremelimumab received by intravenous infusion

Drug: MEDI4736; Drug: tremelimumab

Arm C

EXPERIMENTAL

MEDI4736 and tremelimumab received by intravenous infursion

Drug: MEDI4736; Drug: tremelimumab

Interventions

MEDI4736 DRUG

MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).

Arm A; Arm B; Arm C; Dose Escalation

tremelimumab DRUG

Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).

Arm A; Dose Escalation

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Advanced non-small cell lung cancer
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate organ and marrow function

You may not qualify if:

• Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
• Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs
• Active or prior documented autoimmune disease within the last 2 years.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (69)

Research Site

Birmingham, Alabama, 35294-3300, United States

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Tucson, Arizona, 85715, United States

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Los Angeles, California, 90025, United States

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Los Angeles, California, 90095, United States

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San Francisco, California, 94158, United States

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Aurora, Colorado, 80045, United States

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New Haven, Connecticut, 06510, United States

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Newark, Delaware, 19713, United States

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Tampa, Florida, 33612, United States

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Indianapolis, Indiana, 46202, United States

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Baltimore, Maryland, 21287, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215, United States

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Ann Arbor, Michigan, 48109, United States

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Detroit, Michigan, 48201, United States

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St Louis, Missouri, 63110, United States

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Lebanon, New Hampshire, 03756, United States

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New York, New York, 10032, United States

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New York, New York, 10065, United States

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Huntersville, North Carolina, 28078, United States

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Columbus, Ohio, 43210, United States

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Portland, Oregon, 97213, United States

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Fort Worth, Texas, 76104, United States

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Houston, Texas, 77521, United States

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Tyler, Texas, 75702, United States

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Fairfax, Virginia, 22031, United States

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Seattle, Washington, 98109, United States

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Morgantown, West Virginia, 26506, United States

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Darlinghurst, 2010, Australia

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Gosford, 2250, Australia

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Kogarah, 2217, Australia

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Brussels, 1000, Belgium

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Ghent, 9000, Belgium

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Liège, 4000, Belgium

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Bordeaux, 33076, France

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Dijon, 21079, France

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La Tronche, 38043, France

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Lille, 59000, France

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Lyon, 69008, France

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Marseille, 13385, France

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Montpellier, 34298, France

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Saint-Herblain, 44805, France

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Bologna, 40138, Italy

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Milan, 20141, Italy

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Rozzano, 20089, Italy

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Saronno, 21047, Italy

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Siena, 53100, Italy

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Sondrio, 23100, Italy

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Cheongju-si, 28644, South Korea

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Incheon, 405-760, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 02841, South Korea

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Seoul, 03080, South Korea

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Seoul, 05368, South Korea

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Seoul, 06351, South Korea

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Seoul, 120-752, South Korea

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Seoul, 138-736, South Korea

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Barcelona, 08028, Spain

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Barcelona, 08035, Spain

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Jaén, 23007, Spain

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Madrid, 28034, Spain

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Madrid, 28041, Spain

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Málaga, 29730, Spain

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Seville, 41013, Spain

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Valencia, 46015, Spain

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Tainan, 704, Taiwan

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Taipei, 10048, Taiwan

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London, W1G 6AD, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Related Publications (2)

• Garon EB, Spira AI, Goldberg SB, Chaft JE, Papadimitrakopoulou V, Cascone T, Antonia SJ, Brahmer JR, Camidge DR, Powderly JD, Wozniak AJ, Felip E, Wu S, Ascierto ML, Elgeioushi N, Awad MM. Brief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1-Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial. J Thorac Oncol. 2023 Aug;18(8):1094-1102. doi: 10.1016/j.jtho.2023.04.020. Epub 2023 May 4.

  PMID: 37146752 DERIVED

• Antonia S, Goldberg SB, Balmanoukian A, Chaft JE, Sanborn RE, Gupta A, Narwal R, Steele K, Gu Y, Karakunnel JJ, Rizvi NA. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016 Mar;17(3):299-308. doi: 10.1016/S1470-2045(15)00544-6. Epub 2016 Feb 6.

  PMID: 26858122 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• MedImmune LLC

  MedImmune LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2013
• First Posted: December 4, 2013
• Study Start: October 25, 2013
• Primary Completion: September 17, 2019
• Study Completion: September 17, 2019
• Last Updated: October 31, 2019

Record last verified: 2019-10

Locations

AU (3); TW (2); IT (6); ES (8); BE (3); KR (9); GB (2); US (28); FR (8)