Bispecific Antibody Shows Early, Promising Responses in Trial

PF-06863135, a bispecific antibody being developed by Pfizer as an injectable treatment, shows a manageable safety profile and promising response rates at high dose in heavily pre-treated patients with relapsed or refractory multiple myeloma, according to early data from an ongoing Phase 1/2 trial.

“The very high response rate observed with PF-06863135, coupled with manageable safety and the convenience of subcutaneous [under the skin] administration, underscores the potential impact this medicine may have,” Jeff Settleman, PhD, senior vice president and chief scientific officer at Pfizer Oncology, said in a press release.

These findings were reported in the oral presentation, “Preliminary Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Subcutaneously (SC) Administered PF-06863135, a B-Cell Maturation Antigen (BCMA)-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM),” given at the 62^nd American Society of Hematology (ASH) Annual Meeting and Exposition, held online Dec. 5–8.

PF-06863135, also called PF-3135, is an engineered antibody that acts as a bridge between immune cells and cancer cells by binding to proteins on the surface of both cell types. Specifically, the antibody binds to the CD3 surface receptor on immune T-cells, and to the B-cell maturation antigen (BCMA) on myeloma cells, linking them and activating an immune response.

Part 1, or Phase 1, of Pfizer’s trial (NCT03269136) was a open-label, dose-escalating study testing the safety, tolerability, pharmacokinetics and pharmacodynamics (how a drug moves through and affects the body, respectively) of PF-3135 in adults with myeloma who have relapsed from or are refractory (resistant) to standard therapy.

Eligible patients must have received at least one immunomodulatory agent, one proteasome inhibitor, and one CD38 inhibitor. The trial is recruiting patients at sites across the U.S. and Canada; more information is available here.

Expected to enroll a total of 80 people, the trial is being conducted in two parts. First, participants were given escalating doses of PF-3135 to determine the safest and most effective dose for further studies. Once an optimal dose is established, as it now has been, patients will receive that treatment dose, either alone or in combination with a PD-1 inhibitor or Revlimid (lenalidomide), in Phase 2 (part 2) of the study.

To date, a total of 30 patients have been treated with PF-3135 in weekly doses ranging from 80 to 1,000 micrograms (mcg)/kg — in the Phase 1 trial.

While these people were heavily pretreated, with a median of seven prior lines of therapy, 80% of those given an effective dose (215 mcg/kg or greater) responded to treatment.

Of the 20 patients treated at doses of at least 215 mcg/kg, six had a complete response (no signs of cancer), three had a very good partial response, and six achieved a partial response. Responses were even higher (83%) in the group of six patients receiving the 1,000 mcg/kg dose, which is now the recommended dose for further studies.

The treatment had a manageable safety profile. While most patients experienced side effects, including cytokine release syndrome, a potentially life-threatening reaction cause by an overactive immune system, most of these cases were mild to moderate in severity.

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