Multiple myeloma is still an uncurable cancer, but Johnson & Johnson’s Janssen unit is building a toolkit to fight back.
The latest additions are the bispecific antibodies teclistamab and talquetamab, both being tested in heavily pretreated patients. Janssen will showcase data on both therapies at the American Society of Clinical Oncology (ASCO) meeting in June.
Starting with teclistamab, the CD3 bispecific that was submitted to the FDA back in December 2021, Janssen will reveal updated results from the phase 3 MajesTEC-1 trial, which included patients who had undergone four prior treatments. These data are part of the package that supported the application, according to Janssen’s Craig Tendler, M.D., global head of late clinical development, diagnostics and medical affairs, hematology and oncology, for Janssen R&D.
The ASCO data will showcase an added six months of follow-up data, Tendler said in an interview with Fierce Biotech. Janssen found that at 14 months, the overall response rate is holding up at 64% of patients, with 30% of patients seeing a complete response or better. Previously, Janssen reported an overall response rate of 62% at eight months.
As for safety, a low incidence of grade 3 cytokine release syndrome, or CRS, was noted in teclistamab-treated patients as well as a very low rate of neurotoxic events, according to Tendler. These are both common adverse events with this type of therapy.
The event was common, however, with 72% of patients experiencing CRS, but only 0.6% were grade 3 and no grades 4 or 5 were reported. None of the enrolled patients had to have their dose reduced as a result of adverse events. The most common events were neutropenia, which is an overabundance of a type of white blood cell and occurred in 65% of patients, and anemia in 50% of patients.
In a separate study to be profiled at ASCO, Janssen is also showing what teclistamab can do in combination with approved multiple myeloma med Darzalex, a Janssen staple in its oncology lineup. In the phase 1b TRIMM-2 trial, the combo showed an overall response rate of 78% in the 37 patients who were eligible for evaluation as of the January cutoff date, while 27 patients, or 73%, had a good partial response or better. Patients in the study had previously received at least three lines of treatment.
The combination trial is an attempt to put up an all-immunotherapy approach to treating the disease, Tendler noted. “We can potentially replace the need for other agents, like for example, pomalidomide, in that setting,” he said, speaking of Bristol Myers Squibb’s Pomalyst.
But the real goal for the combo study is to help Janssen make the case for moving teclistamab up in the line of therapies. Teclistamab has shown that it can destroy the BCMA myeloma cells and achieve minimal residual disease.
The plan is to put the therapy head-to-head against common triple therapies in multiple myeloma, Tendler said. Trials are expected to begin soon for this effort.
“Ultimately, when you have very active single agents in myeloma, bringing them forward almost always is able to demonstrate even a larger benefit than waiting until patients accumulate more and more mutations and become very resistant,” Tendler said.
Meanwhile, the FDA is mulling teclistamab's first approval application as a later-line treatment. The therapy was granted breakthrough-therapy designation, which means Janssen has been working closely with the agency throughout teclistamab’s development.
“Our expectation is with this data and of course, continued follow up with long duration of response that we're seeing here, our hope is that we will reach a positive conclusion by the PDUFA date,” Tendler said.
In yet another data drop from Janssen’s bispecific multiple myeloma program, the ASCO crowd will hear about some phase 1 data on talquetamab from a trial called MonumenTAL-1. The study also enrolled heavily pretreated patients. The readout will include results from the 400 mg and 800 mg groups. The therapy achieved a response rate of 70% in the 400-mg group and 65% in the 800-mg cohort. Very good partial response was observed in 57% and 52% of patients in the 400-mg and 800-mg cohorts, respectively.
Safety was similar to the teclistamab trial, with a low incidence of CRS and neurotoxicity; however, CRS was one of the most common adverse events, along with low white blood cells. These events generally resolved within a week.
The data show that both doses of talquetamab are very effective and the therapy could ultimately have a best-in-class safety profile for this patient population, Tendler said.
Teclistamab and talquetamab will help create a toolbox of therapies to offer multiple myeloma patients.
“The way we look at it is that multiple myeloma, unfortunately, still remains an incurable disease, and for the most part, most of these patients are going to go through various treatment regimens and need multiple options,” Tendler said.
So if a patient has already received a BCMA-targeted agent, talquetamab might be an option. Or if a patient similarly hasn’t received a BCMA targeted agent and can’t get to a treatment center with access to a CAR-T like Janssen’s Carvykti, doctors may turn to teclistamab. Janssen recently received approval for Carvykti, which was developed in partnership with Legend Biotech.
“The bottom line is, we don't look at these as competing agents. They provide good options for patients in various settings, and we know that there is no single regimen that's gonna cure these patients,” Tendler said. “But the goal is to really build potentially curative regimens with both of these agents to hopefully change that sort of paradigm of multiple myeloma remaining an incurable disease.”