AMG 701 Demonstrates Manageable Safety, Favorable Pharmacokinetic Profile in Patients with Relapsed, Refractory Multiple Myeloma

A study evaluating AMG 701, a bi-specific T-cell engager (BiTE) molecule, in relapsed or refractory multiple myeloma (RRMM) found that the drug has a manageable safety profile, encouraging activity levels, and a favorable pharmacokinetic profile in patients with heavily pre-treated disease.

The results, presented at the American Society of Hematology 2020 Meeting and Exposition, support further evaluation of AMG 701, according to the poster. In the study, patients with multiple myeloma that is relapsed, refractory, or intolerant to 3 or more lines of treatment received AMG 701 intravenous infusions weekly in 4-week cycles until disease progression. A 0.8 mg step dose was added prior to target doses of 1.2 mg or more to prevent severe cytokine release syndrome, and target dose was achieved by day 8 or sooner with earlier escalation.

As of July 2, 2020, 75 patients received AMG 701, with a median age of 63 years, a median time since diagnosis of 5.9 years, and a median of 6 prior lines of therapy. Furthermore, 27% of patients had extramedullary disease, 83% had prior stem cell transplant, and 93% had prior treatment with anti-CD38 antibodies. Of the 75 participants, 47 discontinued treatment for disease progression, 4 discontinued due to adverse events, 4 withdrew consent, 1 decided to try a different therapy, 1 withdrew due to investigator discretion, and 1 withdrew due to central nervous system disease. Seventeen patients remain on AMG 701.

The most common hematological adverse events (AEs) were anemia, neutropenia, and thrombocytopenia. The most common non-hematological AEswere cytokine release syndrome, diarrhea, fatigue, and fever. There were 4 deaths from AEs, none related to AMG 701.

The authors noted that the 6.5 mg, 9 mg, and 12 mg doses were expanded. At the 6.5 mg dose, the overall response rate (ORR) was 40%; the ORR was 50% at the 9 mg dose; and the ORR was 29% at the 12 mg dose. Interestingly, the authors said the majority of responses in these doses occurred during the escalation phase, although they noted that there were only 2 responders in total at the 3 dose levels. Based on these findings, the authors concluded that AMG 701 demonstrates positive results in patients with heavily pre-treated RRMM. They added that the study supports further evaluation of the treatment.

REFERENCE

A Phase 1 First in Human (FIH) Study of AMG 701, an Anti-B-Cell Maturation Antigen (BCMA) Half-Life Extended (HLE) BiTE (bispecific T-cell engager) Molecule, in RRMM. Paper presented at: American Society of Hematology 62nd Annual Meeting & Exposition; December 5-8, 2020. Accessed December 3, 2020.