Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma (MonumenTAL-1) MONUMENTAL-1

What's the purpose of this trial?

The purpose of this study is to characterize the safety of Talquetamab and to determine the recommended Phase 2 dose(s) (RP2Ds) and dosing schedule assessed to be safe for Talquetamab (Part 1 [Dose Escalation]) and to further characterize the safety of Talquetamab at the recommended Phase 2 dose(s) (RP2Ds) (Part 2 [Dose Expansion]).

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
  • Part 1: Participants with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies. Part 2: Participants with multiple myeloma measurable by central laboratory assessment who have progressed on, or could not tolerate, all available established therapies; Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram per 24 hours (mg/24 h) or light chain multiple myeloma without measurable disease in the serum or the urine: serum immunoglobulin free light chain (FLC) >= 10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio; If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (Beta human chorionic gonadotropin [beta-hCG]) or urine
  • Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, and is willing to and able participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

Exclusion Criteria:

  • Participants who received or plan to receive any live, attenuated vaccine within 4 weeks prior to the first dose, during treatment, or within 4 weeks of the last dose of Talquetamab. Non-live or non-replicating vaccines approved or authorized for emergency use (example, coronavirus disease [COVID]-19) by local health authorities are allowed
  • Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
  • Received a cumulative dose of corticosteroids equivalent to greater than or equal to ( >=) 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
  • An allogenic stem cell transplant within 6 months before first dose of study drug. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD); and/or an autologous stem cell transplant less than or equal to (<=) 12 weeks before first dose of study drug
  • Documented history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required

Additional Trial Information

Phase 1

Enrollment: 320 patients (estimated)

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Published Results

Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1

May 16, 2022

As of May 16, 2022, 288 pts with no prior exposure to T-cell redirecting therapies had received talquetamab at the RP2Ds in phase 1 or 2. In 143 pts treated at 0.4 mg/kg QW (median time since diagnosis: 6.7 years), median age was 67 years (range 46–86), pts received a median of 5 prior LOT (range 2–13), 31.1% had high-risk cytogenetics, 23% had extramedullary disease, 19.6% had ISS stage 3 disease, 100%/74% were triple-class exposed/refractory, and 73%/29% were penta-drug exposed/refractory; median follow-up was 11.0 months (range 0.5+–26.1). Baseline characteristics were similar among 145 pts who received 0.8 mg/kg Q2W (median follow-up: 5.1 months [range 0.2+–17.9]).

In 143 pts treated at 0.4 mg/kg QW, ORR was 73% (≥VGPR: 58%; ≥CR: 29%). Responses were durable and deepened over time (Figure). Median time to response was 1.2 months (range 0.2–5.0). Median time to CR was 2.1 months (range 1.1–12.4). Median DOR was 9.3 months (95% CI, 6.6–20.2; range 1–23+). Median PFS was 7.5 months (95% CI, 5.7–9.2 [38% censored]). ORRs in pts who were triple-class refractory (72% [76/106]) and penta-drug refractory (71% [30/42]) were comparable to the overall population. Efficacy at 0.8 mg/kg Q2W will be presented at the meeting.

The most common AEs at 0.4 mg/kg QW/0.8 mg/kg Q2W were CRS (79%/72%; grade 3: 2%/1%; grade 4: 0%/0%), dysgeusia (48%/46%; grade 3/4: not applicable [NA]), and anemia (45%/39%; grade 3: 31%/25%; grade 4: 0%/0%]); skin-related AEs occurred in 56%/68% (grade 3: 0%/1%; grade 4: NA) and nail disorders in 52%/43% (grade 3: 0%/0%; grade 4: NA) of patients. Cytopenias, including neutropenia in 34%/28% (grade 3: 20%/17%; grade 4: 10%/6%) and thrombocytopenia in 27%/27% (grade 3: 10%/8%; grade 4: 10%/8%), were generally limited to the first few cycles. At 0.4 mg/kg QW/0.8 mg/kg Q2W, infections occurred in 57%/50% of pts (grade ≥3: 19%/13%); 4.9%/6.2% discontinued, 8.4%/13.8% had dose delays, and 14.7%/6.2% had dose reductions due to AEs. There were 2 deaths due to COVID-19 (1 patient at each RP2D).

Updated Phase 1 Results from MonumenTAL-1: First-in-Human Study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma

December 11, 2021

As of July 19, 2021, 95 patients have received SC talquetamab. The RP2D was originally identified as a weekly SC dose of 405 µg/kg talquetamab with step-up doses. However, alternative dosing schedules that require less frequent administration continue to be investigated. A biweekly RP2D was also identified as an SC dose of 800 µg/kg talquetamab with step-up doses.

30 patients received the 405 µg/kg weekly dosing schedule (median age: 61.5 years [range 46–80]; 63% male; 100% triple-class exposed; 80% penta-drug exposed; 77% triple-class refractory, 20% penta-drug refractory; 30% prior BCMA-directed therapy; median follow-up: 7.5 mo [range 0.9–15.2]). 23 patients received the 800 µg/kg biweekly dosing schedule (median age: 60.0 years [range 47–84]; 48% male; 96% triple-class exposed; 70% penta-drug exposed; 65% triple-class refractory, 22% penta-drug refractory; 17% prior BCMA-directed therapy; median follow-up 3.7 mo [range 0.0–12.0]).

There were no treatment discontinuations due to AEs at either of the RP2Ds. The most common AEs at the 405 µg/kg weekly dose were CRS (73%; 1 patient had grade 3 CRS), neutropenia (67%; grade 3/4: 60%), and dysgeusia (60%; grade 2: 29%); skin-related AEs occurred in 77% (all grade 1/2; nail disorders: 30%) of patients, and infections occurred in 37% of patients (1 patient had grade 3 COVID-19 pneumonia). The most common AEs at the 800 µg/kg biweekly dose were CRS (78%; all grade 1/2), dry mouth (44%; all grade 1/2), and neutropenia (44%; grade 3/4: 35%); skin-related AEs occurred in 65% of patients (grade 3: 13%; nail disorders: 17%) and infections occurred in 13% of patients (1 patient had grade 3 pneumococcal sepsis).

In 30 response-evaluable patients treated with the 405 µg/kg weekly dose, the overall response rate (ORR) was 70% (very good partial response or better [≥VGPR] rate: 57%). In 17 response-evaluable patients treated with the 800 µg/kg biweekly dose, the ORR was 71% (≥VGPR rate: 53%). Responses were durable and deepened over time in both cohorts (Figure). Median duration of response (DOR) was not reached at either RP2D; the 6-month DOR rate for patients who received the 405 µg/kg weekly dose was 67% [95% CI: 41–84]. Serum trough levels of talquetamab were comparable at both RP2Ds. Consistent with the mechanism of action for talquetamab, pharmacodynamic data from cohorts treated at both dose levels showed peripheral T-cell activation and induction of cytokines.

Updated results of a phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM)

May 28, 2021

  • As of Feb 8, 2021, 174 pts received talquetamab, 102 by IV and 72 by SC; in parts 1 and 2, 28 pts were treated at the RP2D, identified as weekly SC 405 µg/kg, with 10.0 and 60.0 µg/kg step-up doses.
  • Patients treated at the RP2D had a median age of 61.5 y (range 46–80) and a median of 5.5 prior lines of therapy (range 2–14; 100%/79% triple-class/penta-drug exposed; 71%/18% triple-class/penta-drug refractory; 86% refractory to last line of therapy; 21% with prior B-cell maturation antigen–directed therapy).
  • No dose-limiting toxicities occurred at the RP2D in part 1.
  • Most common AEs at the RP2D were:
    • CRS (79%; grade 3 4%; median time to onset: day after SC injection),
    • neutropenia (64%; grade 3/4 54%),
    • anemia (57%; grade 3/4 29%) and
    • dysgeusia (57%; all grade 1/2);
    • infections were reported in 32% of patients (grade 3/4 4%) and neurotoxicity in 7% (grade 3/4 0).
  • In all, 75% of pts dosed at the RP2D had skin-related AEs (grade 3/4 0), including 18% with nail disorders.
  • The overall response rate at the RP2D in response-evaluable pts (n = 24) was 63%, with 50% reaching very good partial response or better; 9/17 (53%) evaluable triple-class refractory pts and 3/3 (100%) penta-drug refractory pts had a response.
  • Median time to first confirmed response at the RP2D was 1.0 mo (range 0.2–3.8); responses were durable and deepened over time (median follow-up 6.2 mo [range 2.7–9.7+] for responders at the RP2D).
  • At the RP2D, exposure was maintained over the maximum EC90 target level from an ex vivo cytotoxicity assay, and consistent T cell activation was seen.
A Phase 1, First-in-Human Study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D (GPRC5D) x CD3 Bispecific Antibody, in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)Clinically Relevant Abstract

December 02, 2020

As of 20 Jul 2020, 137 pts had received talquetamab; 102 by IV (0.5 – 180 µg/kg) and 35 by SC (5 – 800 µg/kg) dosing. Median age was 64 years (33 – 80; 31% were ≥70) and 22% had ISS stage III disease at study entry. Median number of prior therapies was 6 (2 – 20) over a median of 6.5 years (0.9 – 27) since diagnosis, 85% were refractory to last line of therapy, 79% triple-class refractory, 73% penta-drug exposed, and 31% penta-drug refractory. 13 (10%) pts had received selinexor and 21 (15%) had prior BCMA-directed therapy.

Most frequently reported all grade AEs were anemia (50%), CRS (47%), neutropenia (45%), and lymphopenia (40%). Most common grade 3 – 4 AEs were lymphopenia (37%), anemia (27%), and neutropenia (25%). CRS was mostly grade 1 – 2 except for 5 pts with grade 3 CRS (˂8% of pts with CRS) that occurred with IV dosing; only grade 1 – 2 CRS was seen with SC dosing. CRS was generally confined to the first cycle with median time to onset of 1 day (1 – 3) for IV and 2 days (1 – 5) for SC dosing. Treatment-related neurotoxicity was reported in 7 (5%) pts (all resolved/resolving; median duration of 2 days [1 – 9]): 4 had grade 1 – 2 events and 3 had grade 3 events of delirium (n=1), decreased level of consciousness (n=1), or confusion (n=1). Six of 7 pts had neurotoxicity that occurred in the context of CRS, including all 3 grade 3 events. Infections were reported in 37% of pts (8% grade 3 – 4). Infusion related reactions (IV; 15%) and injection site reactions (SC; 14%) were grade 1 – 2 and generally occurred in cycle 1. Two dose-limiting toxicities were observed: clinically asymptomatic grade 4 increased lipase in the setting of a pancreatic plasmacytoma (7.5 µg/kg IV) and grade 3 maculopapular rash (135 µg/kg SC). The maximum tolerated dose (MTD) has not been defined.

Overall response rate (ORR) for IV doses of 20 – 180 µg/kg was 78% (14/18; 2 pending confirmation); 6/6 responded at the 60 µg/kg IV dose. ORR for SC doses of 135 – 405 µg/kg was 67% (8/12); 3/4 responded at the 405 µg/kg SC dose. Responses were noted starting at 1.0 µg/kg, were rapid at a median of 1 month (0.2 – 3), and durable with median not reached in 36/46 (4 pts with response 15+ months; longest at 23+ months). Data at higher doses are immature, and results will be updated at the meeting.

Trial Locations

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University of Alabama at Birmingham O'Neal Comprehensive Cancer Center at UAB

Birmingham, AL

Open and Accepting


City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

New York

Mount Sinai Hospital Tisch Cancer Institute

New York, NY

Open and Accepting

New York University Langone Medical Center Laura and Isaac Perlmutter Cancer Center

New York, NY

Open and Accepting


Sarah Cannon TriStar Centennial Medical Center

Nashville, TN

Open and Accepting
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