Modular Phase 2 Study to Link Combination Immune-therapy to Patients With Advanced Solid and Hematologic Malignancies. Module 9: PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies.
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Small Cell Lung Cancer
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 76
- Locations
- 20
- Primary Endpoint
- Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this signal seeking study is to determine whether treatment with PDR001 and LAG525 demonstrates sufficient efficacy in advanced malignancies to warrant further study.
Detailed Description
This was a phase II, open-label study to determine the efficacy and safety of treatment with the combination of PDR001+LAG525 across multiple tumor types that are relapsed and/or refractory to available standard of care therapies. There were 7 tumor cohorts assessed: 1) Small cell lung cancer, 2) Gastric/esophageal adenocarcinoma, 3) Castration resistant prostate adenocarcinoma (CRPC), 4) Soft tissue sarcoma, 5) Ovarian adenocarcinoma, 6) Advanced well-differentiated neuroendocrine tumors and 7) Diffuse large B cell lymphoma (DLBCL). Participants were treated with the combination of PDR001 300 mg with LAG525 400 mg once every 3 weeks (Q3W) via intravenous (i.v.) infusion. Participants received study treatment for a maximum of 2 years, or until disease progression (assessed by investigator per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma criteria (Cheson et al 2007)), unacceptable toxicity, death or discontinuation from study treatment for any other reason.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients eligible for inclusion in this study had to meet all of the following criteria:
- •Patient must have had at least one prior line of therapy for their disease and must not be beyond 4th progression/relapse of disease (5 maximum prior lines).
- •Patient has a pathology confirmed diagnosis of a solid tumor or lymphoma listed in the section "condition". Patients must have measurable disease as per appropriate guidelines (Solid Tumors by RECIST 1.1 and Diffuse Large B-cell Lymphoma by Revised Response Criteria for Malignant Lymphoma - Cheson et al 2007).
Exclusion Criteria
- •Patients eligible for this study must not meet any of the following criteria:
- •History of severe hypersensitivity reactions to other monoclonal antibodies.
- •Impaired cardiac function or clinically significant cardiac disease.
- •Active, known or suspected autoimmune disease or a documented history of autoimmune disease within three years prior to screening with a few exceptions as per protocol.
- •Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
- •Patient with second primary malignancy within \< 3 years of first dose of study treatment.
- •Prior immunotherapy treatment with PD-1, PD-L1, CTLA-4, or LAG-3 antibodies.
Outcomes
Primary Outcomes
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma
Time Frame: 24 weeks
CBR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) and Stable Disease (SD). Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. CBR (CR+PR+SD) is reported overall and by tumor type.
Secondary Outcomes
- Progression-Free Survival (PFS)(From start of treatment to first documented progression or death, assessed up to 113 weeks)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From first dose of study treatment until last dose of study treatment plus 150 days post treatment, assessed up to 135 weeks.)
- Duration of Response (DOR)(From first documented response (CR or PR) to first documented progression or death, assessed up to 113 weeks)
- Dose Intensity(From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.)
- Overall Response Rate (ORR)(From start of treatment until end of treatment, assessed up to 113 weeks)
- Time to Progression (TTP)(From start of treatment to first documented progression or death due to underlying cancer, assessed up to 113 weeks)
- Time to Response (TTR)(From start of treatment to the first documented response of either complete response or partial response, assessed up to 113 weeks)
- Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug(From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.)