A Study of Nivolumab in Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Relapsed/Refractory Primary Testicular Lymphoma (PTL)

A Phase 2, Open-label, Single-arm, Two-cohort Study of Nivolumab in Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) or Relapsed/Refractory Primary Testicular Lymphoma (PTL)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02857426

Acronym

CheckMate 647

Enrollment

Registered

2016-08-05

Start date

2016-10-21

Completion date

2020-11-24

Last updated

2021-12-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma

Brief summary

The purpose of this study is to determine whether Nivolumab is effective in the treatment of Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Relapsed/Refractory Primary Testicular Lymphoma (PTL)

Interventions

DRUGNivolumab

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Pathologically confirmed PCNSL or PTL who failed or did not respond to at least 1 line of systemic therapy * Measurable disease requirements on scans: PCNSL subjects should have at least one measurable extranodal brain lesion; PTL subjects should have at least 1 measurable extranodal lesion or nodal lesion * Have tumor tissue for PD-L1 expression testing * Must have a Karnofsky performance status of 70-100

Exclusion criteria

* a) Intraocular PCNSL without evidence of brain disease b) PCNSL patients who cannot undergo MRI assessments c) PCNSL patients with systemic disease * Patients with certain diseases such as active autoimmune disease, type I diabetes, hypothyroidism that needs hormone replacement, active infection, psychiatric disorder * Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast * Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways PCNSL, and PTL subjects with brain or spinal cord lesion who have received doses of more than 2 mg/day of dexamethasone or equivalent within the 14 days period prior to the first dose of nivolumab are excluded Other protocol defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
BICR-Assessed Objective Response Rate (ORR)	Up to approximately 51 months	Percentage of participants with a confirmed objective response rate (ORR) by blinded independent central review (BICR) assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.

Secondary

Measure	Time frame	Description
BICR-Assessed Progression Free Survival (PFS)	Up to approximately 51 months	Progression-free survival (PFS) is defined as the time from first dosing date to the date of the first documented progression using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.
Investigator-Assessed Objective Response Rate (ORR)	Up to approximately 51 months	Percentage of participants with a confirmed objective response rate (ORR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.
Investigator-Assessed Duration of Response (DOR)	Up to approximately 51 months	Duration of response (DOR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the time from first response (CR or PR) to the date of initial objectively documented progression as determined using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.
Overall Survival (OS)	Up to approximately 51 months	Overall survival (OS) was analyzed and reported for both PCNSL and PTL patient populations. OS is defined as the time from first dosing date to the date of death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive.

Countries

Brazil, Canada, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Russia, Singapore, United States

Participant flow

Pre-assignment details

47 PCNSL participants treated. 19 PTL participants treated.

Participants by arm

Arm	Count
PCNSL Cohort Nivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.	47
PTL Cohort Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.	19
Total	66

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse event unrelated to study drug	6	2
Overall Study	Completed treatment	0	2
Overall Study	Death	1	0
Overall Study	Disease progression	34	13
Overall Study	Maximum clinical benefit	1	0
Overall Study	Participant withdrew consent	1	1
Overall Study	Study drug toxicity	4	1

Baseline characteristics

Characteristic	PTL Cohort	Total	PCNSL Cohort
Age, Continuous	66.7 Years STANDARD_DEVIATION 8.6	66.1 Years STANDARD_DEVIATION 9.6	65.9 Years STANDARD_DEVIATION 10.1
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants	44 Participants	33 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants	21 Participants	13 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	5 Participants	15 Participants	10 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) White	12 Participants	49 Participants	37 Participants
Sex: Female, Male Female	0 Participants	20 Participants	20 Participants
Sex: Female, Male Male	19 Participants	46 Participants	27 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	32 / 47	13 / 19
other Total, other adverse events	40 / 47	16 / 19
serious Total, serious adverse events	33 / 47	15 / 19

Outcome results

Primary

BICR-Assessed Objective Response Rate (ORR)

Percentage of participants with a confirmed objective response rate (ORR) by blinded independent central review (BICR) assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.