TRiMM-2: Response Rate of 78% Seen in Patients Who Receive Talquetamab With Subcutaneous Daratumumab for Multiple Myeloma

Updated results from the phase 2 TRiMM-2 study reported Saturday at the American Society of Clinical Oncology (ASCO) showed an overall response rate of 78% in patients with multiple myeloma who were treated with a combination of talquetamab and subcutaneous daratumumab.

Lead investigator Bhagirathbhai R. Dholaria, MD, assistant professor of medicine in the Department of Hematology-Oncology at Vanderbilt University Medical Center, explained during an oral abstract session—and in an interview with The American Journal of Managed Care®—how the immunomodulatory effects of the 2 therapies could create a synergy to treat multiple myeloma.

“Daratumumab is one of the most effective therapies for newly diagnosed or relapsed/refractory multiple myeloma. And one of the important immunomodulatory effects of datatumumab is actually that it also depletes the CD38 expressing regulatory T cell,” he said in the interview.

“The hope was that you can potentially improve the efficacy of talquetamab, which relies on the host T cell function to attack the cancer and control the myeloma. If you combine both of these together, maybe you can potentiate the antimyeloma activity of talquetamab.”

Talquetamab received Breakthrough Therapy status nearly a year ago and is being studied both as a monotherapy and in combination with other drugs; as Dholaria explained during the session, it appears that blood counts are preserved with this combination, making talquetamab, “a potentially good partner” that can combine well with other therapies to treat multiple myeloma.

That’s important, because for all the success over the past decade in identifying new treatments for multiple myeloma, it does not have a cure, so the hunt is always on for more options, especially for patients who have received multiple lines of therapy. In 2023, an estimated 35,000 people in the United States are expected to be diagnosed with multiple myeloma, and more than 12,000 will die from the disease.

TRiMM-2 included patients who were treated with 3 prior lines of therapy, including anti-CD38, BCMA-targeted, and T-cell redirecting therapies. Patients were treated with 0.4 mg/kg or 0.8 mg/kg of talquetamab every 2 weeks, with step-up doses in addition to subcutaneous daratumumab. Results report Saturday showed the following:

• The overall response rate was 78%, and responses deepened over time.
• Responses were seen in 84% (42 of 50 patients) in the 0.8 mg/kg arm, including 74% who achieved a very good partial response or better; 16% with a complete response and 36% had a stringent complete response.
• The overall response rate among patients previously treated with an anti-CD38 antibody was 82.2% (37/45) and 78.9% (15/19) among patients with prior T-cell redirection therapy in 0.8 mg/kg cohort.
• With a median follow-up of 16.8 months, 71.4% (10/14) of those in treated weekly with the 0.4 mg/kg dose achieved a response, 57.1% percent achieved a very good response or better, 14.3% reached a complete response, and 28.6% achieved a stringent complete response.
• For patients treated weekly with the 0.4 mg/kg dose, response rates for those previously treated with an anti-CD38 antibody were 63.6 percent (7/11), and the overall response rate was 66.7% (4/6) for those with prior treatment with T-cell redirection therapy.
• Median time to onset of cytokine release syndrome (CRS) was 1 day, with a median duration of 2 days; 63% of patients had infections, 22% were grade 3 or 4. There were 3 deaths, 2 for pneumonia and 1 possibly related to the study treatment. ICANS occurred in 3 patients, all grade 1 or 2 and resolved in 2 days or less.

At the time of data cutoff, 65.4% of responders were still on therapy, and median duration of response was 20.3 months on the 0.8 mg/kg dose given every 2 weeks, and not reached among those taking the 0.4 mg/kg dose weekly. Median progression-free survival (PFS) was 19.4 months for those taking the higher dose every 2 weeks and not reached for those on the lower dose taken weekly; 12-month median PFS rate was 67.4% and 77.4%, respectively. Median overall survival was not reached in either arm.

Both talequetamab and subcutaneous daratumumuab, sold as Darzalex, are made by Janssen Pharmaceuticals.

Additional Results for MonumenTAL-1

Combined data for 288 patients taking talquetamab presented in December at the American Society of Hematology meeting in New Orleans, Louisiana, showed that more than 70% of patients with multiple myeloma saw responses that deepened over time.

Updated results for the phase 1/2 MonumenTAL-1 study, now totaling 339 patients, were treated with subcutaneous talquetamab at the recommended phase 2 dose of 0.8 mg/kg biweekly or 0.4 mg/kg weekly with step-up doses. The overall response to talquetamab was similar at both doses. After a median follow-up of 12.7 months, 71.7% of response-evaluable patients treated at the higher dose at 2-week intervals achieved a response, and 60.7% achieved a very good partial response or better, with 9% achieving a complete response and 29.7% a stringent complete response.

After a median follow-up of 18.8 months, 74.1% of response-evaluable patients taking the lower weekly dose saw a 59.4% very good partial response or better, with a 9.8% complete response and a 23.8% stringent complete response.

Median duration of response was not reached for those on the larger, biweekly dose and was 9.5 months for those on the smaller, weekly dose. The 12-month PFS rates were 54.4% percent, 34.9% and 38.1%, respectively.

Discontinuation rates due to adverse events were low—8% at the larger dose and 5% at the smaller dose. Common AEs at both doses were CRS, which was comparable (74.5% at the larger dose and 79% at the smaller dose), but rates of grade 3 or higher were low (0.7% for the larger dose, 2.1% for the smaller dose). Other common AEs above 70% were dysgeusia (all grade 1 and 2), skin-related AEs, 73.1% for the larger dose only. Safety profile was manageable. There were no talquetamab-related deaths.

Jordyn Sava contributed to this report.

References

1. Dholaria BR, Weisel K, Mateos MV, et al. Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Updated TRIMM-2 results. J Clin Oncol. 2023; 41(suppl 16): abstr 8003. DOI: 10.1200/JCO.2023.41.16_suppl.8003

2. Schinke C, Touzeau C, Minnema MC, et al. Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(suppl 16);abstr 8036. DOI:10.1200/JCO.2023.41.16_suppl.8036