Clinical trialPhase 1Multiple myeloma

Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma

N Engl J Med · 2022232 patients (102 with IV dosing and 130 with subcutaneous dosing)

Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NW, Rodríguez-Otero P, et al. N Engl J Med. 2022. 387:2232-2244

Study type: Clinical trial
Study name: MonumenTAL-1
Phase: Phase 1
Design: Phase 1 dose-escalation study to determine the recommended phase 2 dose
Sample size: 232 patients (102 with IV dosing and 130 with subcutaneous dosing)
Source: N Engl J Med · 2022
Trial registration: NCT03399799

In plain words

Talquetamab is a drug that steers the body's immune cells (T cells) towards cancerous myeloma cells so that they destroy them. In this study it was given to patients whose multiple myeloma had come back after many treatments or had not responded to treatment, and about 64 to 70 percent of patients responded at the recommended doses. Common side effects included fever and inflammation-like symptoms caused by the release of cytokines (immune messenger proteins), skin problems and changes in taste; most of these were mild to moderate.

Key results

70%

Response rate, 405 µg/kg weekly (median follow-up 11.7 months)

95% CI 51–85

64%

Response rate, 800 µg/kg every two weeks (median follow-up 4.2 months)

95% CI 48–78

10.2 months (405 dose) and 7.8 months (800 dose)

Median duration of response

77% (405 dose) and 80% (800 dose)

Cytokine release syndrome

All but one event were grade 1 or 2

67% (405 dose) and 70% (800 dose)

Skin-related events

63% (405 dose) and 57% (800 dose)

Taste disturbance (dysgeusia)

Dose and schedule cards

Talquetamab monotherapy (MonumenTAL-1 trial)

Relapsed or refractory myeloma after at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibodyOn the page “Multiple myeloma” · Relapsed myeloma: CAR T-cell therapy and bispecific antibodies

Relapsed or refractory myeloma after at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody

Drug	Dose	Route	Schedule
Weekly schedule
Talquetamab	0.01 mg/kg (Day 1), 0.06 mg/kg (Day 4), 0.4 mg/kg (Day 7); then 0.4 mg/kg weekly	SC	Step-up doses on Days 1, 4 and 7; then weekly (at least 6 days apart)
Every-2-week schedule
Talquetamab	0.01 (Day 1), 0.06 (Day 4), 0.4 (Day 7) and 0.8 mg/kg (Day 10); then 0.8 mg/kg every 2 weeks	SC	Step-up doses on Days 1, 4, 7 and 10; then every 2 weeks (at least 12 days apart)

Cycle length: Weekly or every 2 weeks
Duration: Until disease progression or unacceptable toxicity

Per the FDA label for TALVEY: hospitalisation for 48 hours after all step-up doses; 1–3 hours before each step-up dose: dexamethasone 16 mg, diphenhydramine 50 mg and acetaminophen 650–1,000 mg. Skin and nail toxicities and dysgeusia are characteristic of this drug.

On the page “Multiple myeloma” · Relapsed myeloma: CAR T-cell therapy and bispecific antibodies

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Intravenous talquetamab

Talquetamab IV, weekly or every two weeks, at doses of 0.5 to 180 µg/kg body weight (102 patients). Further dosing details are in the full text.

2Subcutaneous talquetamab

Talquetamab subcutaneously, weekly, every two weeks or monthly, at doses of 5 to 1600 µg/kg (130 patients).

3Recommended phase 2 dose: 405 µg/kg weekly

Talquetamab subcutaneously, 405 µg/kg weekly (30 patients).

4Recommended phase 2 dose: 800 µg/kg every two weeks

Talquetamab subcutaneously, 800 µg/kg once every two weeks (44 patients).

Source of the regimen details: Abstract of the paper

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with heavily pretreated relapsed or refractory multiple myeloma whose disease had progressed on standard therapies (median of 6 prior lines of therapy) or who could not receive these therapies without unacceptable side effects.

Endpoints

Primary endpoints: frequency and type of dose-limiting toxicities (part 1 of the study only), adverse events and laboratory abnormalities; these were assessed to select recommended doses for the phase 2 study. Response and duration of response were also reported.

Safety and side effects

At the two recommended subcutaneous phase 2 doses, common adverse events included cytokine release syndrome (77% and 80%), skin-related events (67% and 70%) and dysgeusia (63% and 57%). All but one cytokine release syndrome event were grade 1 or 2. One dose-limiting toxicity, a grade 3 rash, was reported in a patient who received the 800 µg dose level.

Clinical significance and place in guidelines

This phase 1 study showed that talquetamab produces substantial responses in heavily pretreated relapsed or refractory multiple myeloma, and two subcutaneous doses were selected for evaluation in phase 2. The drug's place in therapy and the status of approvals and guidelines should be checked separately, as the abstract does not address them.

Limitations

Phase 1 study without a control group. Follow-up in the 800 µg/kg group was short (median 4.2 months) and the number of patients in each recommended-dose group was small (30 and 44 patients). Duration of response and long-term outcomes are not yet definitive with this limited follow-up.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.