A Phase 1b Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer (D4190C00006)
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ClinicalTrials.gov Identifier: NCT02000947 |
Recruitment Status :
Completed
First Posted : December 4, 2013
Last Update Posted : October 31, 2019
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
NSCLC Non-small Cell Lung Cancer Lung Cancer | Drug: MEDI4736 Drug: Tremelimumab Drug: tremelimumab | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 459 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | October 25, 2013 |
Actual Primary Completion Date : | September 17, 2019 |
Actual Study Completion Date : | September 17, 2019 |
Arm | Intervention/treatment |
---|---|
Experimental: Dose Escalation
MEDI4736 and tremelimumab received by intravenous infusion.
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Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: Tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb). |
Experimental: Arm A
Medi4736 and tremelimumab received by intravenous infusion
|
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: Tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb). |
Experimental: Arm B
MEDI4736 and tremelimumab received by intravenous infusion
|
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb). |
Experimental: Arm C
MEDI4736 and tremelimumab received by intravenous infursion
|
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb). |
- 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.
- 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
- 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
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Ages Eligible for Study: | 18 Years to 101 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age ≥ 18 years
- Advanced non-small cell lung cancer
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Adequate organ and marrow function
Exclusion Criteria:
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT02000947
Study Director: | MedImmune LLC | MedImmune LLC |
Responsible Party: | MedImmune LLC |
ClinicalTrials.gov Identifier: | NCT02000947 |
Other Study ID Numbers: |
D4190C00006 2015-003715-38 ( EudraCT Number ) |
First Posted: | December 4, 2013 Key Record Dates |
Last Update Posted: | October 31, 2019 |
Last Verified: | October 2019 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
anti-CTLA-4 anti-PD-L1 immunotherapy IMTC |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic |
Bronchial Neoplasms Durvalumab Tremelimumab Antibodies, Monoclonal Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs |