A Study of Talquetamab for People With Multiple Myeloma Who Have Received BCMA CAR T-Cell Therapy

Inclusion Criteria

• •Patient with multiple myeloma who has received prior treatment with an IMID, PI, and a CD38 monoclonal antibody
• •Received treatment with an FDA approved BCMA CART cell therapy ide-cel within 1-3 months prior to enrollment
• •Serum monoclonal protein \< 0.5 gm/dL; 24-hour urine monoclonal protein \< 200 mg; and serum involved free light chains \< 10 mg/dL
• •No evidence of disease progression based on IMWG criteria
• •≥18 years of age at the time of signing informed consent.
• •ECOG performance status of 0 or 1
• •Recovered to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding Grade 2 neuropathy and Grade 2 alopecia.
• •No evidence of ongoing, any grade cytokine release syndrome or immune effector cell mediated neurotoxicity
• •No additional myeloma therapies after the CART cell therapy
• •Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 without growth factor support for 7 days for G-CSF or GM-CSF and for 14 days for pegylated GCSF prior to the laboratory test.
• •Platelet count ≥ 75,000/mm\^3 (without platelet transfusion or thrombopoietin receptor agonist use in the previous 7 before the laboratory test). Platelets ≥ 50,000/mm\^3 is acceptable if the counts prior lymphodepleting chemotherapy for the preceding CAR T cell therapy was \< 75,000.
• •Hemoglobin ≥ 8 g/dL (without red blood cell transfusion support or erythropoietin use within 7 days of the laboratory test).
• •Creatinine Clearance (CrCl)/estimated glomerular filtration rate (eGFR) ≥ 30 mL/min, measured by 24 hour urine assessment or estimated by CKD-EPI2021.
• •Oxygen saturation ≥ 92% on room air
• •Hepatic Function:
• •* Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
• •* Serum total bilirubin ≤ 2 x ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5 x ULN is required).
• •International ratio (INR) or partial thromboplastin time (PTT) \< 1.5 x ULN
• •Cardiac Function: left ventricular ejection fraction ≥ 45% by echocardiogram (ECHO) or multigated acquisition scan (MUGA).
• •Willing and able to adhere to the study visit schedule and other protocol requirements
• •Female patients of childbearing potential (FCBP) must:
• •* Have a negative highly-sensitive serum β-human chorionic gonadotropin (β-hCG) pregnancy test (\<5 IU/mL) at screening and a negative urine or serum pregnancy test within 24 hours before the first dose of study drug.
• •* Practicing a highly effective, preferably user-independent method of contraception (failure rate of \<1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study drug and until 100 days after last dose.
• •* Agree to pregnancy testing (serum or urine) within 100 days after the last study drug administration.
• •* Agree to use an additional contraceptive method in addition to the requirements listed above
• •* Agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 100 days after the last dose of study drug.
• •* Agree to abstain from breastfeeding from screening through at least 6 months after the last dose of talquetamab
• •Male patients must:
• •* Agree to wear a condom when engaging in any activity that allows for passage of ejaculate to another person, during the study and for 100 days after the last dose of study drug. Male subjects should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak.
• •* Men must agree not to donate sperm for the purpose of reproduction during the study and for at least 100 days after receiving the last dose of study drug.
• •Must sign an ICF (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
• •Seropositive for human immunodeficiency virus (HIV-1). Acute hepatitis A. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (ie, subjects who are HBsAg negative with antibodies to total hepatitis B core antigen \[Anti-HBc\] with or without the presence of hepatitis B surface antibodies \[Anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of HBVDNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (Anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. Active hepatitis C infection as measured by positive hepatitis C virus (HCV)-RNA testing. Subjects with a history of Hepatitis C virus antibody positivity must undergo HCV-RNA testing
• •Prior malignancies except resected basal cell carcinoma or treated carcinoma in situ. Cancer treated with curative intent less than 5 years prior to enrollment will not be allowed unless approved by the PI. Cancer treated with curative intent greater than 5 years prior to enrollment is allowed.
• •Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma. The only allowed exceptions are:
• •* Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured
• •* Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
• •* Noninvasive cervical cancer treated within the last 24 months that is considered completely cured
• •* Localized prostate cancer (N0M0):
• •* With a Gleason score of ≤6, treated within the last 24 months, or untreated and under surveillance
• •* With a Gleason score of 3+4 that has been treated \>6 months prior to full study screening and considered to have a very low risk of recurrence
• •* History of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
• •* Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence
• •* Other malignancy that is considered cured with minimal risk of recurrence.
• •Female patients who are breastfeeding or who intend to become pregnant during participation in the study or until 100 days after the last dose of therapy.
• •Participant plans to father a child while enrolled in this study or within 100 days after the last dose of study treatment.
• •Known allergy or hypersensitivity to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• •Serious medical of psychiatric illness likely to interfere with participation on this clinical study
• •Uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
• •Acute diffuse infiltrative pulmonary disease requiring home oxygen therapy
• •Unwilling or unable to provide informed consent
• •Unable or unwilling to return to the center for treatment and follow up