PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies

Small Cell Lung Cancer Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03365791
• Other study ID #: CPDR001XUS01
• Status: Completed
• Phase: Phase 2
• Start date: January 24, 2018
• Est. completion date: September 17, 2020

Study information

• Verified date: May 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: September 17, 2020
• Est. primary completion date: February 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Well-differentiated Neuroendocrine Tumors
• Castration Resistant Prostate Adenocarcinoma
• Diffuse Large B Cell Lymphoma
• Esophageal Adenocarcinoma
• Gastric Adenocarcinoma
• Hematologic Neoplasms
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Neoplasms
• Neuroendocrine Tumors
• Ovarian Adenocarcinoma
• Sarcoma
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Soft Tissue Sarcoma

Intervention

Biological:
• PDR001
PDR001 is a high-affinity, ligand-blocking, humanized anti-programmed death-1 (PD-1) IgG4 antibody that blocks the binding of Programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) to PD-1.
• LAG525
LAG525 is a high-affinity, ligand-blocking, humanized anti-LAG-3 IgG4 antibody which blocks the binding of the known LAG-3 ligand MHC class II to LAG-3.

Locations

Country	Name	City	State
United States	University Cancer and Blood Center, LLC	Athens	Georgia
United States	Weinberg Cancer Institute at Franklin Square Hospital	Baltimore	Maryland
United States	Billings Clinic Dept of Billings Clinic(2)	Billings	Montana
United States	Northwestern University Medical School	Chicago	Illinois
United States	University of Illinois Cancer Center at Chicago SC	Chicago	Illinois
United States	The University of Kansas Clinical Research Center	Fairway	Kansas
United States	Oncology Consultants Oncology Consultants	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics Comprehensive Cancer Center	Iowa City	Iowa
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Providence Regional Cancer System SC	Lacey	Washington
United States	Comprehensive Cancer Centers	Las Vegas	Nevada
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Oncology Hematology West Nebraska Cancer Specialists	Omaha	Nebraska
United States	Illinois Cancer Care P.C. Jesse Brown VA	Peoria	Illinois
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Oregon Health and Science University	Portland	Oregon
United States	California Pacific Medical Center Drug Shipment (2)	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma	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.	24 weeks
Secondary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). 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.; ORR (CR+PR) is reported overall (including all tumor types).	From start of treatment until end of treatment, assessed up to 113 weeks
Secondary	Time to Response (TTR)	TTR is defined as the time from the date of first dose to the date of first documented response of Complete Response (CR) or Partial Response (PR). In case of solid tumor if a patient did not achieve a confirmed response they were censored at maximum follow-up for patients who had a PFS event (progressed or died due to any cause), or at last adequate tumor assessment date otherwise.; 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).	From start of treatment to the first documented response of either complete response or partial response, assessed up to 113 weeks
Secondary	Duration of Response (DOR)	DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time between the date of first documented response (CR or PR) and the date of first documented progression/relapse or death due to any cause within 150 days of the last study drug dose date. If a patient not had an event, duration was censored at the date of last adequate tumor assessment.; 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).	From first documented response (CR or PR) to first documented progression or death, assessed up to 113 weeks
Secondary	Time to Progression (TTP)	TTP is the time from start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient not had an event, time to progression was censored at the date of last adequate tumor assessment.; 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).	From start of treatment to first documented progression or death due to underlying cancer, assessed up to 113 weeks
Secondary	Progression-Free Survival (PFS)	PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 150 days of the last dose. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.; 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).	From start of treatment to first documented progression or death, assessed up to 113 weeks
Secondary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with AEs and SAEs including changes in laboratory parameters, vital signs and ECGs qualifying and reported as AEs.	From first dose of study treatment until last dose of study treatment plus 150 days post treatment, assessed up to 135 weeks.
Secondary	Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug	Number of participants with at least one dose interruption of PDR001 and LAG525 and number of participants with permanent dose discontinuation of PDR001 and LAG525.	From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.
Secondary	Dose Intensity	Dose intensity (mg/day) of PDR001 and LAG525 is calculated as cumulative dose in milligrams divided by duration of exposure in days.	From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.

External Links

•   A Plain Language Trial Summary is available on novctrd.com