Pfizer Reports Positive Data for Multiple Myeloma Antibody Drug

December 11, 2020 - Pfizer recently announced that 83 percent of patients in the ongoing Phase 1 study of its investigational multiple myeloma antibody drug achieved clinical response at the highest dose level. 

The bispecific antibody, PF-06863135, elicited an overall response rate of 80 percent among 20 patients treated in cohorts across efficacious dose ranges of 215 to 1,000 micrograms/kilograms weekly.

Out of the 20 patients, six saw stringent complete response or complete response, three achieved “very good” partial response, and six achieved partial response, Pfizer said.

Additionally, three patients had received at least one BCMA-targeted therapy prior to the Phase 1 study. 

“The very high response rate observed with PF-06863135, coupled with manageable safety and the convenience of subcutaneous administration, underscores the potential impact this medicine may have for people living with this devastating disease,” Jeff Settleman, senior vice president and chief scientific officer of oncology R&D at Pfizer, said in the announcement.   

“These findings support continued development of PF-06863135 for people with multiple myeloma, both as monotherapy and in combination with standard or novel therapies,” he continued. 

Pfizer stated that PF- 06863135 is designed to bind to BCMA, which is highly expressed on the surface of multiple myeloma cells and the CD3 receptor found on the surface of cancer-fighting T cells.

Binding these two cells together may enable stronger T-cell-mediated anti-myeloma activity. 

Researchers enrolled a total of 30 patients with relapsed or refractory multiple myeloma in the Phase 1 study. They found that PF-06863135 elicited no dose-limiting toxicities across the dose levels evaluated. 

Additionally, cytokine release syndrome was reported in 73.3 percent of patients and was limited to grade 1 (56.7 percent) or grade 2 (16.7 percent). Grade 3 or higher adverse events occurred in over 10 percent of patients.

These adverse events included lymphopenia (53.3 percent of enrollees), neutropenia (26.7 percent), thrombocytopenia (16.7 percent), and anemia (16.7 percent).  

Researchers noted that based on the positive data and the minor adverse events, 1,000 micrograms/kilograms weekly is currently the recommended Phase 2 dose.

According to the latest numbers, there are approximately 32,270 new cases of multiple myeloma diagnosed annually in the US and 160,000 globally.  

The first treatment approved for multiple myeloma was cyclophosphamide under the name Cytoxan, in 1959. Since then, various top pharmaceutical companies have launched multiple myeloma drugs, over 40 of which have been approved for use in infected patients. 

Back in 2014, Takeda Pharmaceutical announced that FDA approved bortezomib, known under the brand of VELCADE, for the treatment of adult patients with multiple myeloma. 

Specifically, the 2014 Phase 2 trial showed a 38.5 percent overall response in multiple myeloma patients who had been previously treated with a VELCADE-based regimen and relapsed at least six months after completion. 

Then in June of this year, Sanofi announced that its monoclonal antibody, Sarclisa, added to carfilzomib and dexamethasone, reduced the risk of relapsed multiple myeloma progression or death in patients compared to standard care.

The trial found that out of 302 patients, the Sarclisa combination therapy met primary endpoint at the pre-planned interim analysis. 

At the end of August, Genmab also announced that FDA approved the use of its drug, DARZALEX in combination with carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who previously received lines of therapy. 

Specifically, the combination of DARZALEX’s daratumumab, carfilzomib, and dexamethasone was approved in two carfilzomib dosing regimens, 70 mg/m² once weekly and 56 mg/m² twice weekly, the company said. 

Despite available treatments, multiple myeloma remains incurable and is associated with significant patient burden. Since the disease does not have a cure, most patients will relapse.