Janssen Releases Data on Teclistamab as Monotherapy, Combined With Darzalex Faspro

The Janssen Pharmaceutical Companies of Johnson & Johnson presented poster presentations featuring data on teclistamab as a monotherapy and in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro) at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Applications seeking approval of teclistamab are under health authority review in Europe and the United States.

In one poster, initial results were presented from cohort C of the MajesTEC-1 study evaluating teclistamab for the treatment of individuals with relapsed or refractory multiple myeloma (RRMM) who were previously exposed to an anti-BCMA treatment. The individuals had received 6 prior lines of therapy, with 85% triple-class refractory and 35% penta-drug refractory.

The use of teclistamab, following prior treatment with chimeric antigen receptor T cell (CAR-T) therapy and/or an antibody drug conjugate (ADC) targeting BCMA, resulted in promising response rate in patients with heavily pretreated RRMM. At a median follow-up of 12.5 months, the overall response rate (ORR) was 52.5% among 40 individuals who received teclistamab in cohort C.

Responses to teclistamab occurred early and deepened over time with comparable response rates in individuals previously treated with ADC and/or CAR-T.

Investigators reported a tolerable safety profile in individuals previously treated with anti-BCMA treatment with no discontinuations or dose reductions because of adverse events. The safety profile was comparable with that observed in individuals who were BCMA treatment-naïve with no new safety signals.

In the 12.5-month follow-up, 65% of individuals had infections. Additionally, the most common AE was cytokine release syndrome (CRS), with a median time to CRS onset and duration of 2 days and 2 days, respectively. Other AEs were anemia, lymphopenia, neutropenia, and thrombocytopenia.

In a second presentation, investigators presented study results that analyzed patient-reported assessments of quality-of-life metrics among individuals in the MajesTEC-1 trial who had received their first treatment dose by March 18, 2021.

The metrics analysis included function, including cognitive, emotional, and physical; generic health, including ability to engage in usual activities, anxiety, depression, discomfort, mobility, pain, and self-care; symptoms, including constipation, diarrhea, fatigue, loss of appetite, nausea, pain, and vomiting,; and

Investigators found that 80% of the 110 individuals included in the patient-reported outcomes (PRO) analysis noted meaningful improvement, which is the percentage of individuals with clinically meaningful change from the baseline on at least 1 of the symptom scales. The reduction in pain scores occurred as early as cycle 2.

Additionally, to date, no meaningful improvement was observed in the scales for fatigue and physical functioning. The initial PRO results complement recent clinical data and supported teclistamab as a potential off-the-shelf, T-cell redirecting therapy for individuals with RRMM.

As of September 7, 2021, the median duration of treatment was 5.7 months and median follow-up was 7.8 months. The global health status scores significantly improved from baseline at cycles 4, 6, and 8, and the emotional functioning significantly improved at all time points.

The PRO assessments included European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 item. Additionally, the PROs were assessed on day 1 of each treatment cycle of 28 days.

Additional follow-up is needed to assess the full benefit of meaningful improvement in functional outcomes, investigators said.

Additionally, updated results from the phase 1 TRIMM-2 study were featured during a poster session at the 2022 ASCO Annual Meeting, which evaluated teclistamab in combination with daratumumab and hyaluronidase-fihj.

Daratumumab and hyaluronidase-fihj is a CD38-firected monoclonal antibody approved to be given subcutaneously for the treatment of individuals with multiple myeloma.

In the study, individuals received a median 5 prior lines of therapy. Approximately 75% had prior exposure to anti-CD38 therapies, and approximately 63.1% were refractory to anti-CD38 treatment.

Individuals who were evaluated achieved an ORR of 76.5% at a median follow-up of 8.6 months.

Another poster presentation for the multicenter, ongoing, open-label, phase 3, randomized MajesTEC-3 study compared the efficacy of teclistamab in combination with daratumumab in combination with pomalidomide and dexamethasone or bortezomib dexamethasone in individuals with RRMM.

Additional data from both the talquetamab and the teclistamab cohorts of the TRIMM-2 study were featured as oral presentations at the European Hematology Association 2022 Congress, which took place June 9, 2022, to June 12, 2022.

Reference

Updated data for Janssen’s bispecific teclistamab suggest continued deep and durable responses in the treatment of patients with relapsed or refractory multiple myeloma. Johnson and Johnson. News release. June 5, 2022. Accessed June 9, 2022. https://www.jnj.com/updated-data-for-janssens-bispecific-teclistamab-suggest-continued-deep-and-durable-responses-in-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma