A Study of Talquetamab and Teclistamab Each in Combination With a Programmed Cell Death Receptor-1 (PD-1) Inhibitor for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of the study is to identify the safe dose(s) of a PD-1 inhibitor in combination with talquetamab or teclistamab, and to characterize the safety and tolerability of talquetamab or teclistamab when administered in combination with a PD-1 inhibitor.

Detailed Description
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Multiple myeloma is a malignant plasma cell disorder that accounts for approximately 10 percent (%) of all hematologic cancers, making it the second most common hematologic malignancy. The overall rationale of this study is that talquetamab or teclistamab in combination with a PD-1 inhibitor may lead to enhanced clinical responses in treatment of relapsed or refractory multiple myeloma through multiple mechanisms of action. The study will evaluate the clinical hypothesis that talquetamab or teclistamab can be safely administered at the selected dose when combined with a PD-1 inhibitor. The study will consist of a screening period, treatment period (Part 1: dose escalation and Part 2: dose expansion) and a post treatment follow-up. End of study is defined as last study assessment for last participant in study. Total duration of study is up to 2 years 5 months. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points.

Official Title
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A Phase 1b Study of Bispecific T Cell Redirection Antibodies in Combination With Checkpoint Inhibition for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma

Conditions
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Relapsed/ Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: Talquetamab
* Drug: Teclistamab
* Drug: PD-1 Inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria Participants with relapsed or refractory disease that are not a candidate for available therapy with established clinical benefit Have measurable disease at screening as defined by at least 1 of the following: a) Serum M-protein level greater than or equal to (>=) 0.5 grams per deciliter (g/dL); b) Urine M-protein level >= 200 milligrams (mg) per 24 hours; c) Light chain multiple myeloma: Serum immunoglobulin (Ig) free light chain (FLC) >= 10 milligrams/deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Exclusion Criteria: Prior antitumor therapy within 21 days prior to the first dose of study treatment (proteasome inhibitor [PI] therapy or radiotherapy within 14 days, immunomodulatory drug (IMiD) agent therapy within 7 days, gene -modified adoptive cell therapy or autologous stem cell transplant within 3 months) Prior therapy with PD-1 inhibitors, allogeneic stem cell transplant or solid organ transplant Active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary light chain amyloidosis Active Central Nervous System (CNS) involvement or exhibition of clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required Live, attenuated vaccine within 4 weeks before the first dose of study treatment Non-hematologic toxicity from prior anticancer therapy that has not resolved to baseline levels or to Grade less than or equal to (<=) 1 (except alopecia [any grade] or peripheral neuropathy to Grade <= 2) Received a cumulative dose of corticosteroids equivalent to >= 140 milligrams (mg) of prednisone within the 14-day period before the start of study treatment administration

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation<br>Participants will receive either talquetamab (treatment regimen A) or teclistamab (treatment regimen B) with a PD-1 inhibitor biweekly. | Drug: Talquetamab<br>* Talquetamab will be administered as a subcutaneous (SC) injection.<br>Drug: Teclistamab<br>* Teclistamab will be administered as a SC injection.<br>Drug: PD-1 Inhibitor<br>* The PD-1 inhibitor will be administered as an intravenous injection.<br>|
| Experimental: Part 2: Dose Expansion<br>Participants will receive either treatment regimen A or treatment regimen B with a PD-1 inhibitor at the dose levels identified in Part 1. | Drug: Talquetamab<br>* Talquetamab will be administered as a subcutaneous (SC) injection.<br>Drug: Teclistamab<br>* Teclistamab will be administered as a SC injection.<br>Drug: PD-1 Inhibitor<br>* The PD-1 inhibitor will be administered as an intravenous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to 2 years 5 months | 
| Number of Participants with Adverse Events (AEs) by Severity | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event. | Up to 2 years 5 months | 
| Number of Participants with Abnormalities in Clinical Laboratory Assessments | Number of participants with abnormalities in clinical laboratory assessments (serum chemistry and hematology) will be reported. | Up to 2 years 5 months | 
| Number of Participants with Dose-Limiting Toxicity (DLTs) | The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. | Up to 2 years 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants who achieve partial response (PR) or better according to the International Myeloma Working Group (IMWG) 2016 criteria. | Up to 2 years 5 months | 
| Very Good Partial Response (VGPR) or Better Response Rate | VGPR or better response rate is defined as the percentage of participants who achieve a VGPR or better response (stringent complete response [sCR]+ complete response [CR]+VGPR) according to the IMWG 2016 criteria. | Up to 2 years 5 months | 
| Complete Response (CR) or Better Response Rate | CR or better response rate is defined as the percentage of participants who achieve a CR or better response (sCR+CR) according to the IMWG 2016 criteria. | Up to 2 years 5 months | 
| Stringent Complete Response (sCR) Rate | sCR rate is defined as the percentage of participants who achieve an sCR according to the IMWG 2016 criteria. | Up to 2 years 5 months | 
| Duration of Response | Duration of response is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG 2016 criteria or death due to any cause, whichever occurs first. | Up to 2 years 5 months | 
| Time to Response | Time to response is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participant has met all criteria for PR or better. | Up to 2 years 5 months | 
| Serum Concentrations of Talquetamab | Serum samples will be analyzed to determine concentrations of Talquetamab using validated, specific, and sensitive immunoassay methods. | Up to 2 years 5 months | 
| Serum Concentrations of Teclistamab | Serum samples will be analyzed to determine concentrations of Teclistamab using validated, specific, and sensitive immunoassay methods. | Up to 2 years 5 months | 
| Serum Concentrations of PD-1 Inhibitor | Serum samples will be analyzed to determine concentrations of PD-1 inhibitor using validated, specific, and sensitive immunoassay methods. | Up to 2 years 5 months | 
| Number of Participants with Anti-Talquetamab Antibodies | Number of participants with anti-talquetamab antibodies will be reported. | Up to 2 years 5 months | 
| Number of Participants with Anti-Teclistamab Antibodies | Number of participants with anti-teclistamab antibodies will be reported. | Up to 2 years 5 months | 
| Number of Participants with Anti-PD-1 Inhibitor Antibodies | Number of participants with anti-PD-1 inhibitor antibodies will be reported. | Up to 2 years 5 months |