Teclistamab, a soon-to-be-approved bispecific antibody, demonstrates its promise in Multiple Myeloma during ASCO 2022

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ASCO 2022: Teclistamab for Multiple Myeloma

Latest teclistamab findings presented at the ASCO 2022 Annual Meeting demonstrate a profound and long-lasting response (Abstract # 8007, 8013, and 8032)

Mechanism of Action: Bispecific IgG4 antibody that binds BCMA and CD3 to redirect T-cells to multiple myeloma cells

Teclistamab is a bispecific antibody that targets BCMA [B-cell maturation agent] and CD3. BCMA is highly expressed on myeloma cells and has limited expression on normal tissue, making it an ideal target for anti-myeloma strategies. The company is also pursuing Teclistamab for regulatory approval in the United States and Europe. At ASCO 2022, Janssen Pharmaceutical presented updated efficacy and safety data from the ongoing Phase I/II MajesTEC-1 trial (NCT03145181: Phase I, and NCT04557098: Phase II).

Moreover, the company presented the results Phase I TRIMM-2 study (NCT04108195), in which teclistamab is being investigated in combination with Darzalex Faspro (daratumumab and hyaluronidase-fihj) in a poster presentation (Abstract #8032). The MajesTEC-1 trial is a multicohort, open-label, Phase I/II study looking at the safety and effectiveness of teclistamab in patients with relapsed/refractory multiple myeloma who have had at least three prior lines of treatment.

By March 2022, 165 patients had received teclistamab at the recommended subcutaneous Phase II dose of 1.5 mg/kg, followed by step-up doses of 0.06 and 0.3 mg/kg in both Phase I (NCT03145181) and Phase II (NCT04557098) of the trial.

Abstract #8007

The data from the MajesTEC-1 study in Multiple Myeloma Patients who have experienced three or more prior lines of therapy were presented at ASCO 2022. Patients with triple class exposed multiple myeloma had an overall response rate (ORR) of 63% after a median follow-up of 14.1 months, with a complete response (CR) or better achieved in 39.4% of patients.

Although response duration data is not yet complete, the median duration of response at this time is 18.4 months and has not been reached in patients who obtained a CR or better. This data shows that teclistamab-induced responses were long-lasting and intensified with time.

The median PFS (progression-free survival) was 11.3 months. Longer follow-up data revealed no additional safety signs. The most prevalent grade 3/4 hematologic AEs were neutropenia, anemia, lymphopenia, and thrombocytopenia, according to 14.1-month follow-up data reported at ASCO 2022 teclistamab data.

Abstract #8013

Initial data from Cohort C of the MajesTEC-1 Study of Teclistamab in Patients with Relapsed/Refractory Multiple Myeloma with Prior Exposure to BCMA Targeted Treatment. The company also released the first data from Cohort C of the MajesTEC-1 research, which looked at teclistamab in treating patients with relapsed/refractory multiple myeloma who had previously been treated with an anti-BCMA.

Cohort C obtained an ORR of 52.5% after a median follow-up of 12.5 months. According to the findings, responses to teclistamab were early and deepened with time, with comparable response rates in patients previously treated with Antibody-drug conjugates (ADCs) and CAR-T. Furthermore, in patients who had previously received anti-BCMA medication, no dosage reductions or discontinuations were owing to adverse events (AEs).

Abstract #8032

Janssen also shared updated findings from the Phase I TRIMM-2 trial (NCT04108195), which is testing Teclistamab in combination with Darzalex Faspro. This trial's findings were presented in a poster session at ASCO 2022 (Abstract #8032). Patients in the study had a median of five prior lines of therapy; 75.4% had previously undergone anti-CD38 treatments, and 63.1% were resistant to anti-CD38 treatment. Evaluable patients had an ORR of 76.5% after a median follow-up of 8.6 months.

Apart from abstracts 8007, 8013, and 8032, the company also revealed preliminary patient-reported Health-Related Quality of Life Outcomes in Patients with Relapsed/Refractory Multiple Myeloma treated with Teclistamab (Abstract #8033). Along with this, a poster (Abstract #TPS8072) was also presented for the ongoing Phase III MajesTEC-3 study (NCT05083169).

“The MajesTEC-1 study update suggests patients with relapsed or refractory multiple myeloma receiving teclistamab achieved a deep response that was also durable. These longer-term data, notably the overall response rate and progression-free survival, are encouraging in this heavily pretreated patient population”–Expert Opinion.

"The updated data presented at ASCO support the ongoing evaluation of teclistamab as a monotherapy and in combination with standard of care treatments” –Expert Opinion.

Conclusion

CAR T-cell therapy approvals are significant achievements in cancer research, especially Hematologic-malignancies; however, the promising results of these therapies come with their own set of challenges, including manufacturing cost and complexity, the possibility of product failure, and known safety issues. As of now, only a few bispecific antibodies in multiple myeloma have been approved by the US Food and Drug Administration (FDA) for their use in cancer (Amgen’s Blincyto, Janssen’s Rybrevant, and Immunocore’s Kimmtrak).

J&J is certainly stepping up its game in the multiple myeloma treatment landscape by exploring novel therapies. With the new approval of CAR-T treatment (CARVYKTI; February 2022), the company hopes to seize the lead in bispecific antibody entry in multiple myeloma. Teclistamab, one of the most anticipated bispecific antibodies in multiple myeloma, is presently being studied in various monotherapy and combination studies.

The European Medicines Agency (EMA) has designated teclistamab as a PRIority MEdicines (PRIME) in January 2021, while the FDA designated it as a Breakthrough Therapy Designation in June 2021. Janssen's teclistamab is the first BCMA x CD3 bispecific to be submitted for approval in Multiple Myeloma to the FDA and EMA.

Janssen filed a Biologics License Application (BLA) to the FDA in December 2021 requesting approval of teclistamab for the treatment of patients with Relapsed/Refractory Multiple Myeloma and marketing authorization applications (MAA) were submitted to the EMA for teclistamab approval in January 2022. With their investigational drug Talquetamab (JNJ-64407564) for Relapsed/Refractory Multiple Myeloma, J&J is also exploring the GPRC5D target.

Bispecific antibody development is making steady progress in the field of Multiple Myeloma, and the majority of potential candidates are still in the early phases of development. Overall, this type of therapy has high expectations, especially because preliminary safety and effectiveness data have been good. Pfizer (Elranatamab), and Roche (Cevostamab), are among other pharmaceutical behemoths who are investigating bispecific antibodies for multiple myeloma, and it will be fascinating to see which bispecific antibody emerges as victorious in terms of safety/efficacy, revenue generation, and outperforming the existing standard of treatment.

The multiple myeloma patient and market share battle is expected to heat up in the future as bispecific antibodies are likely to compete with recently approved CAR-T cell therapies and the current standard of therapies, which includes some of the blockbuster candidates.

Companies- Oncopeptides, GlaxoSmithKline, Bluebird Bio, Janssen Pharmaceutical, Legend Biotech, AbbVie, Roche (Genentech), Bristol Myers Squibb, Regeneron Pharmaceuticals, Pfizer, Takeda, Amgen, SpringWorks Therapeutics, Adicet Bio, Arcellx, Gracell Biotechnologies, Oricell, Poseida Therapeutics, Precision Biosciences, CRISPR Therapeutics AG, Collectis SA, Allogene Therapeutics, Fortis Therapeutics, Novartis, I-Mab/MorphoSys, Cartesian Therapeutics, CASI Pharmaceuticals, LAVA Therapeutics, and others.