A Phase 1b Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer (D4190C00006)

• ClinicalTrials.gov Identifier: NCT02000947
• Recruitment Status: Completed
• First Posted: December 4, 2013
• Last Update Posted: October 31, 2019
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

Tracking Information

• First Submitted Date: November 27, 2013
• First Posted Date: December 4, 2013
• Last Update Posted Date: October 31, 2019
• Actual Study Start Date: October 25, 2013
• Actual Primary Completion Date: September 17, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 19, 2016)

• Number of subjects reporting adverse events [ Time Frame: Screening through 90 days after the last dose of study medication ]
  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
• Objective response [ Time Frame: At least 24 weeks as compared to baseline ]
  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.
• Number of subjects experiencing dose-limiting toxicities (DLTs) [ Time Frame: 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 ]
  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.

Original Primary Outcome Measures (submitted: November 27, 2013)

Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs) [ Time Frame: 90 days after last dose of combination ]

To determine the maximum tolerated dose of MEDI4736 in combination with tremelimumab in subjects with advanced NSCLC. The primary endpoint is the MTD which is the highest dose within a cohort where no more than 1 out of 6 subjects experience dose-limiting toxicities (DLTs) or the highest protocol-defined dose for each agent in the absence of exceeding the MTD. The primary endpoints for safety assessment include adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results.

Current Secondary Outcome Measures (submitted: February 19, 2016)

• Immunogenicity of tremelimumab in combination with MEDI4736 [ Time Frame: During treatment through study completion, about 2 years ]
  Immunogenicity of MEDI4736 and tremelimumab will include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
• Antitumor activity of tremelimumab in combination with MEDI4736 [ Time Frame: During treatment through study completion, about 2 years ]
  Antitumor activity will include objective response (OR) and disease control (DC) based on RECIST Version 1.1, duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
• Pharmacokinetic parameters [ Time Frame: During treatment through study completion, about 2 years ]
  Assessment of PK of MEDI4736 and tremelimumab will include individual MEDI4736 and tremelimumab concentrations in serum, and PK parameters including peak concentration (Cmax), area under the concentration-time curve (AUC), clearance (CL), and half-life (t½).
• Number of subjects reporting adverse events [ Time Frame: Screening through 90 days after the last dose of study medication ]
  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

Original Secondary Outcome Measures (submitted: November 27, 2013)

• Immunogenicity of tremelimumab in combination with MEDI4736 [ Time Frame: 90 days after last dose of combination ]
  The endpoints for assessment of immunogenicity of MEDI4736 and tremelimumab include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
• Antitumor activity of combination [ Time Frame: 2 years ]
  The endpoints for assessment of antitumor activity include objective response (OR) and disease control (DC), based on Response Evaluation Criteria in Solid Tumors (RECIST) guidelines v1.1 with modifications, duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
• Pharmokinetic parameters [ Time Frame: 90 days after last dose of combination ]
  The endpoints for assessment of PK of MEDI4736 and tremelimumab include individual MEDI4736 and tremelimumab concentrations in serum, and PK parameters including peak concentration (Cmax), area under the concentration-time curve (AUC), clearance (CL), and half-life (t½).

Current Other Pre-specified Outcome Measures (submitted: February 19, 2016)

Biomarkers [ Time Frame: During treatment through study completion, about 2 years ]

To evaluate biomarkers that may correlate with clinical activity of MEDI4736 in combination with tremelimumab

Original Other Pre-specified Outcome Measures (submitted: November 27, 2013)

• Biomarkers [ Time Frame: 90 days after last dose of combination ]
  To evaluate biomarkers that may correlate with clinical activity of MEDI4736 in combination with tremelimumab
• Patient-reported outcomes (PROs) [ Time Frame: 2 years ]
  To evaluate the effect of MEDI4736 and tremelimumab on patient-reported outcomes (PROs) in the dose-expansion phase. Patient-reported outcomes as measured by the pain questionnaire, EORTC QLQ-C30, and NSCLC-specific modules will be summarized descriptively; the change from baseline for domain, subscale scores, and individual items by treatment cohort at each time point and change from baseline will be explored.

Descriptive Information

• Brief Title: A Phase 1b Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer
• Official Title: A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer
• 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).
• Detailed Description: This is a multicenter, open-label, dose-escalation, and dose expansion study of MEDI4736 in combination with tremelimumab to evaluate the safety, tolerability, pharmacokinetic (PK), immunogenicity, and antitumor activity of MEDI4736 in combination with tremelimumab in adult subjects with advanced NSCLC.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• NSCLC
• Non-small Cell Lung Cancer
• Lung Cancer

Intervention

• Drug: MEDI4736
  MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).
• Drug: Tremelimumab
  Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
• Drug: tremelimumab
  Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).

Study Arms

• Experimental: Dose Escalation
  MEDI4736 and tremelimumab received by intravenous infusion.
  Interventions:

  • Drug: MEDI4736
  • Drug: Tremelimumab
• Experimental: Arm A
  Medi4736 and tremelimumab received by intravenous infusion
  Interventions:

  • Drug: MEDI4736
  • Drug: Tremelimumab
• Experimental: Arm B
  MEDI4736 and tremelimumab received by intravenous infusion
  Interventions:

  • Drug: MEDI4736
  • Drug: tremelimumab
• Experimental: Arm C
  MEDI4736 and tremelimumab received by intravenous infursion
  Interventions:

  • Drug: MEDI4736
  • Drug: tremelimumab

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 28, 2017): 459
• Original Estimated Enrollment (submitted: November 27, 2013): 156
• Actual Study Completion Date: September 17, 2019
• Actual Primary Completion Date: September 17, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 101 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, France, Italy, Korea, Republic of, Spain, Taiwan, United Kingdom, United States
• Removed Location Countries: Canada, Germany

Administrative Information

• NCT Number: NCT02000947
• Other Study ID Numbers: D4190C00006; 2015-003715-38 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: MedImmune LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: MedImmune LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MedImmune LLC; MedImmune LLC

• PRS Account: MedImmune LLC
• Verification Date: October 2019