This study is designed to evaluate if treatment with adjuvant nivolumab improves depth of response in patients with relapsed refractory multiple myeloma (RRMM) who achieve a less-than-ideal response to idecaptagene vicleucel.
This is a single arm, two-stage, Phase II of adjuvant nivolumab in patients with RRMM treated with at least 2 prior lines of therapy and are refractory to or intolerant of at least one proteasome inhibitor (PI), one immunomodulatory agent (IMiD), and one anti-CD38 antibody who achieved a sub-optimal response (defined as a VGPR, PR, MR, or SD by IMWG 2016 criteria) to treatment with idecabtagene vicleucel. This study will determine best overall response after 2 cycles of adjuvant nivolumab given every 4 weeks in patient who achieve a sub-optimal response to ide-celon restaging studies \~30 days after infusion. The Investigators will also evaluate for changes in CAR-T cell expansion, persistence of CAR-T cells, and additional toxicity compared to historical controls.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
2 cycles of nivolumab at a dose of 480 mg given over approximately 30-minutes intravenously on Day 1 of each treatment cycle
Levine Cancer Institute
Charlotte, North Carolina, United States
Depth of Response
Depth of response will be determined for each participant post ide-cel with adjuvant nivolumab indicating if their best overall response is a Complete Response (CR) or stringent Complete Response (sCR). The post-ide-cel disease response assessments will be calculated relative to the participant's pre-ide-cel disease assessment parameters. Responses will be determined per IMWG 2016 response criteria.
Time frame: From enrollment to best response; approximately 5 months after initiating nivolumab
Progression Free Survival (PFS)
PFS is defined as the duration of time from ide-cel administration to first occurrence of either progressive disease (PD) or death (from any cause). PD will be objectively determined per IMWG 2016 criteria, where progression date is date of first assessment that identified confirmed PD. If subject died without documented PD, progression date will be death date. For surviving subjects who do not have PD, PFS will be censored at the date of last disease assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, PFS will be censored at the date of last disease assessment prior to commencement of subsequent therapy. Subjects who have an initial PFS event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.
Time frame: From date of ide-cel administration to date of progression or death, or censored as described; assessed for approximately 4 years
Best Overall Response
Best overall response will be determined for each participant as a categorical variable indicating the participant's best overall response achieved after treatment with nivolumab, according to IMWG 2016 response criteria. The levels for best overall response will include PD, SD, MR PR, VGPR, CR, sCR.
Time frame: From enrollment to best response; approximately 5 months after initiating nivolumab
Duration of Response (DoR)
Duration of best response will be calculated for each participant. The duration of best response interval will begin at the first disease assessment date indicating the participant's best response. The timing for progression, death, or censoring will be determined as previously described for PFS.
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Time frame: From date of best response to date of progression or death, or censored as described; assessed for approximately 4 years
Minimal Residual Disease (MRD) Negativity Rate
MRD response will be determined for each participant as a binary variable indicating if the participant achieved a MRD negative status after treatment with nivolumab. MRD negative status will be separately determined at 10-5 and 10-6 sensitivity.
Time frame: approximately 2 months and 5 months after enrollment
Overall Survival
OS is defined as the duration of time from ide-cel administration to the date of death from any cause. Participants who are alive or lost to follow-up at the time of the analysis will be censored at the last known date they were alive.
Time frame: From date of ide-cel administration to date of death, or censored as described; assessed for approximately 4 years