- A combination of two dual-acting antibodies developed by Johnson & Johnson helped reduce or eliminate malignant cells in 84% of multiple myeloma patients in a Phase 1 trial, according to results unveiled ahead of the American Society of Clinical Oncology meeting next week.
- The trial paired the two “bispecific” drugs — an approved medicine known as an Tecvayli and an experimental one called talquetamab — in multiple myeloma patients whose disease progressed after their last line of therapy. The regimen J&J intends to advance into further testing performed the best, with 92% of patients seeing a reduction or elimination of cancerous cells, according to summary results released Thursday.
- The Food and Drug Administration approved Tecvayli last October based on a response rate of 63%. J&J followed two months later with a submission for talquetamab, after up to 70% of patients responded in clinical testing. Patients taking both drugs frequently have an immune-related side effect associated with certain immunotherapies, which prompted the regulator to put restrictions on Tecvayli’s use.
The development of so-called bispecific antibodies has surged in the last few years, with blood cancer drugs like Tecvayli, AbbVie’s Epkinly and Roche’s Lunsumio getting to market and others following close behind. The first bispecific drug, Amgen’s Blincyto, gained approval in 2014 but has only modest sales. Drug companies are hoping for better with newer iterations.
The drugs work by binding simultaneously to proteins on immune cells and cancerous ones, unleashing an attack on tumors. In multiple myeloma, they’re meant to be more convenient alternatives to personalized cell therapies that have proved dramatically effective at treating the condition.
J&J brought the first bispecific medicine to market for multiple myeloma with Tecvayli. Like many others in development, it binds to a protein called BCMA.
With talquetamab, J&J is adding a second dual-acting drug to the mix with a different target, GPRC5D, that’s overexpressed in the bone marrow of myeloma patients. The company believes attacking a second pathway could improve outcomes by overcoming resistance to treatment.
The study, called RedirecTT-1, is the first evidence supporting that theory. It’s enrolling up to 164 patients who have progressed following several treatment regimens and tested multiple doses of the two-drug regimen alongside a third J&J myeloma medicine called Darzalex. As an early trial, the study’s main goals were to evaluate safety and the best dose to take forward, but J&J also looked how well the combination impacted signs of disease.
Summary results released Thursday included data from 63 patients who had received the combination as of Dec. 12, with a median follow-up of just over 14 months since initiating treatment. The overall response rate was 84%, and 34% of the patients who received the combination had a “complete” response, meaning there was no detectable sign of disease. As a single therapy, Tecvayli helped 28% of patients achieve a complete response in clinical testing, while talquetamab had a 34% rate.
Among patients with disease that has spread beyond the bone marrow, 73% responded to treatment and 31% had a complete response.
Treatment was associated with a high level of side effects, including an overreaction of the immune system called cytokine release syndrome, or CRS, that’s often seen with cell therapies. The results show that CRS occurred in 81% of patients, although only 3% of patients had a severe enough case to need hospital care.
Study investigators also reported cases of neutropenia, or low white blood cell counts, judged as Grade 3 or 4 in severity in 75% of patients, and severe instances of anemia in 43%.
Trial researchers intend to include data from 19 more patients when the data are presented at ASCO on June 3.
If talquetamab were approved along with a Tecvayli combination regimen, J&J would have an arsenal of four different multiple myeloma drugs, some of which could be included in co-formulations to protect the company’s franchise, SVB Securities analyst David Risinger wrote in a Feb. 15 note to clients.
J&J executives believe that combination-focused approach will give patients and doctors several new ways to extend survival.
“No one's going to be cured with one treatment," said Craig Tendler, J&J’s head of late-stage clinical development in cancer and blood disorders, in a December interview with BioPharma Dive. “So we see these as really being part of regimens that will be used based upon complementary mechanisms of action,” he added, that coud address “specific patient subgroups and disease characteristics.”