Nivolumab for the Treatment of Relapsed or Refractory Multiple Myeloma in Patients with Sub-optimal Response to Idecabtagene Vicleucel

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information signed by the participant or his/her legally authorized representative.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1 at the time of enrollment. PS must be evaluated within 14 days prior to enrollment.
• Measurable disease according to International Myeloma Working Group [(MWG) 2016 criteria present within 28 days prior to ide-cel infusion. Note that patients will NOT be required to have measurable disease at time of enrollment. Measurable disease is defined as: * Serum M-protein ≥ 1 g/dL (≥ 0.5 g/dL for immunoglobulin A [IgA] or immunoglobulin M [IgM]) OR * Urine M-protein ≥ 200 mg/24 hours (h) OR * Involved free light chain (FLC) level ≥ 10 mg/dL provided serum FLC ratio is abnormal.
• Previous treatment with idecabtagene vicleucel according to the Food and Drug Administration (FDA) approved United States (US) prescribing information with a response of VGPR, PR, MR or SD by IMWG 2016 criteria evaluated no sooner than 3 weeks after idecabtagene vicleucel infusion when compared to baseline disease evaluations collected no earlier than 28 days prior to ide-cel infusion. Note: The 28-day window applies to all assessments, even if assessments were performed on different days. * Note: Participants who received non-conforming idecabtagene vicleucel who were originally prescribed idecabtagene vicleucel according to the FDA approved label may be considered for inclusion per the investigator’s discretion.
• Prior to administration of idecabtagene vicleucel, must have received at least 2 prior lines of therapy for multiple myeloma (MM), and must be refractory to or intolerant of at least one proteasome inhibitor (PI), one immunomodulatory agent (IMiD), and one anti-CD38 antibody (triple class refractory).
• Participants must be enrolled no sooner than 3 weeks and no later than 6 weeks from the date of the idecabtagene vicleucel infusion.
• Recovered from all non-hematologic reversible acute toxic effects of prior therapy (other than alopecia) to ≤ grade 1 or baseline. Participants with grade ≤ 2 treatment induced peripheral neuropathy are eligible. Participants with hematologic reversible acute toxic effects are allowed to participate if laboratory values meet eligibility parameters.
• Absolute neutrophil count (ANC) ≥ 0.5 x 10^3/uL (growth factor support is allowed) (within 28 days prior to enrollment).
• Platelet count ≥ 20 x 10^3/uL (without transfusion support within 48 hours of screening draw) (within 28 days prior to enrollment).
• Hemoglobin (Hgb) ≥ 8g/dL (without transfusion support within 48 hours of screening draw) (within 28 days prior to enrollment).
• Calculated creatinine clearance ≥ 30mL/min calculated per institutional standards (within 28 days prior to enrollment).
• Corrected serum calcium ≤ 12.0 mg/dl (within 28 days prior to enrollment).
• Total bilirubin (TBILI) ≤ 1.5 x upper limit of normal (ULN) (within 28 days prior to enrollment).
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN (within 28 days prior to enrollment).
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN (within 28 days prior to enrollment).
• International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless the participant is receiving anticoagulant therapy, and PT or PTT is within the therapeutic range of intended use of anticoagulants (within 28 days prior to enrollment).
• Females of childbearing potential (FCBP) must have a negative serum pregnancy test within 72 hours prior to enrollment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause). * FCBP must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of < 1% per year when used consistently and correctly) from the time of informed consent until 5 months after last dose of nivolumab. Contraceptive methods with low user dependency are preferable but not required. ** Highly Effective Birth Control Methods *** Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (Hormonal contraception may be susceptible to interaction with the investigational medicinal product [IMP], which may reduce the efficacy of the contraception method) **** Oral **** Intravaginal **** Transdermal *** Progestogen-only hormonal contraception associated with inhibition of ovulation (Hormonal contraception may be susceptible to interaction with the investigational medicinal product [IMP], which may reduce the efficacy of the contraception method) **** Oral **** Injectable **** Implantable *** Intrauterine device (IUD) **** Contraception methods that in the context of this guidance are considered to have low user dependency *** Intrauterine hormone-releasing system (IUS) **** Contraception methods that in the context of this guidance are considered to have low user dependency *** Bilateral tubal occlusion **** Contraception methods that in the context of this guidance are considered to have low user dependency *** Vasectomised partner **** Contraception methods that in the context of this guidance are considered to have low user dependency **** Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the FCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success *** Sexual abstinence **** In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant
• Ability of the participant to understand and comply with study procedures for the entire length of the study, as determined by the enrolling investigator.

Exclusion Criteria

• Diagnosis of Waldenstrom macroglobulinemia, polyneuropathy organomegaly monoclonal-protein skin changes (POEMS) syndrome, or amyloidosis.
• History of/or active infection listed below: * Active infection requiring systemic therapy (NOTE: at discretion of investigator, participants receiving treatment for an uncomplicated urinary tract infection or localized cellulitis may be eligible.) * Uncontrolled human immunodeficiency virus (HIV) or hepatitis B infection. Well controlled HIV infection (as defined by an undetectable viral load) and chronic hepatitis B infection on appropriate prophylaxis can be considered per enrolling investigator discretion * Active hepatitis C infection. Participants with previously treated hepatitis C infection with documented eradication of their infection will be allowed to enroll * Known history of active TB (bacbillus tuberculosis).
• Pregnant or breastfeeding (Note: breast milk cannot be stored for future use while the mother is being treated on study.).
• Current evidence of active cytokine release syndrome or neurotoxicity (any grade).
• Participants previously diagnosed with an additional malignancy must be disease-free for at least 2 years prior to enrollment. Exceptions include basal cell or squamous cell skin cancer and in situ cervical or bladder cancer.
• Treatment with any anti-myeloma therapy or investigational drug within 30 days prior to cycle 1 day 1 of nivolumab other than ide-cel with the exception of lymphodepleting chemotherapy or steroids for ide-cel therapy. Investigational includes drugs approved for human use but not approved for the indication.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator.
• History of transplant: * Autologous stem cell transplant within 12 weeks of cycle 1 day 1 (C1D1) * Allogeneic stem cell transplant * Solid organ transplant.
• Active known or suspected autoimmune disease. Participants with type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Known history of interstitial lung disease or known history of non-infectious pneumonitis.
• Inability to take Pneumocystis jirovecii (PJP) prophylaxis (either trimethoprim-sulfamethoxazole, dapsone, or pentamidine).
• A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of C1D1 (Note: Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease).
• Prisoners or participants who are involuntarily incarcerated.
• Known history of myocarditis, regardless of etiology.
• Known history of allergy or hypersensitivity to study drug components.
• History of serious side effects to nivolumab or ipilimumab, as defined by the enrolling investigator.