A Sequential Cohort Study Comparing Kappamab Alone to Kappamab, Lenalidomide and Low Dose Dexamethasone in Kappa-Restricted Relapsed Refractory Multiple Myeloma (AMaRC 01-16)

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.3144-3144
• Main Authors: Kalff, Anna, Shortt, Jake, Yuen, Flora, Reynolds, John, Quach, Hang, Wallington-Beddoe, Craig Thomas, Walker, Patricia, Harrison, Simon, Dunn, Rosanne, Spencer, Andrew
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-130084

BACKGROUND: KappaMab is a chimeric IgG1 monoclonal antibody specific for Kappa Myeloma antigen (KMA), a tumour specific cell antigen exclusively expressed on the surface of kappa restricted MM cells. Early safety and efficacy signals seen with single-agent treatment in phase I/II studies in conjunction with observations that IMiD®-treatment upregulates the KMA target and enhances effector cell cytotoxicity, provide rationale for this proof-of principal immune-oncology (IO) approach in a kappa restricted MM population. AIMS: To establish the clinical benefit rate (CBR) of KappaMab alone (Stage 1) and in combination with lenalidomide (LEN) and low dose dexamethasone (DEX) (Stage 2). Secondary aims: to determine the safety of KappaMab in combination with LEN and DEX, in particular, the incidence of immunological adverse events (AEs); to evaluate kinetics of response (time to response [TTOR], PFS, OS). METHODS: Investigator initiated, phase IIb, multi-centre, open label sequential cohort study comparing KappaMab alone to KappaMab in combination with LEN and DEX in relapsed/refractory (RR) MM. Key inclusion criteria were kappa-restricted MM, 1-3 prior lines of therapy but no prior LEN. Recruitment was planned for 60 patients, with an initial intention to treat 30 patients per stage. In Stage 1, patients received KappaMab (10mg/kg IV infusion) weekly for 8/52 (induction), then every 4/52 (maintenance). [One cycle = 28d] For Stage 2, KappaMab dosing was as per stage 1 with the addition of LEN (25mg D1-21) and DEX 40mg weekly. In cycle 1 of Stage 2, LEN and DEX commenced 1/52 prior to KappaMab. [Cycle 1 = 35d: LEN 25mg D1-28 and DEX 40mg weekly (D1, 8, 15, 22, 29)]. Treatment continued until toxicity/progression. This is a planned interim analysis of the primary endpoint (CBR). RESULTS: Recruitment has completed (n=59), however only 40 patients are included in this analysis (Table 1), enrolled between November 2016 and January 2019. Following review by the DMC, recruitment to Stage 1 was terminated early (n=19). 40 patients have commenced treatment in Stage 2, however only the first 21 are included in this analysis: 14/21 had prior thalidomide (refractory =3), 19/21 had prior proteasome inhibitor (PI) (bortezomib = 19, ixazomib = 5; PI refractory = 7), 3/21 were double refractory. 12/40 patients remain on study (Stage 1=1, Stage 2=11). 20 patients have progressed (Stage 1=14, Stage 2=6), 6 withdrew consent (3 each stage), 1 other and 5 have died (Stage 1=2, Stage