A SEQUENTIAL COHORT STUDY COMPARING KAPPAMAB ALONE TO KAPPAMAB, LENALIDOMIDE AND LOW DOSE DEXAMETHASONE IN KAPPA-RESTRICTED RELAPSED REFRACTORY (RR) MULTIPLE MYELOMA (AMARC 01-16)
Author(s): ,
Anna Kalff
Affiliations:
Clinical Haematology,Alfred Hospital-Monash University,Melbourne,Australia
,
Jake Shortt
Affiliations:
School of Clinical Sciences,Monash University,Melbourne,Australia;Monash Haematology,Monash Health,Melbourne,Australia
,
Flora Yuen
Affiliations:
Clinical Haematology,Alfred Health-Monash University,Melbourne,Australia
,
John Reynolds
Affiliations:
Alfred Health and Faculty of Medicine, Nursing and Health Sciences,Monash University,Melbourne,Australia
,
Hang Quach
Affiliations:
Haematology,St Vincents Hospital,Melbourne,Australia;Faculty of medicine,University of Melbourne,Melbourne,Australia
,
Craig Wallington-Beddoe
Affiliations:
Centre for Cancer Biology,University of South Australia and SA Pathology,Adelaide,Australia;College of Medicine and Public Health,Flinders University,Bedford Park,Australia;School of Medicine,University of Adelaide,Adelaide,Australia
,
Patricia Walker
Affiliations:
Clinical Haematology,Peninsula Health,Frankston,Australia;Clinical Haematology,Alfred Health-Monash University,Melbourne,Australia
,
Simon Harrison
Affiliations:
Clinical Haematology,Peter MacCallum Cancer Centre and Royal Melbourne Hospital,Melbourne,Australia;Sir Peter MacCallum department of Oncology,University of Melbourne,Melbourne,Australia
,
Rosanne Dunn
Affiliations:
HaemaLogiX Pty Ltd,Sydney,Australia
Andrew Spencer
Affiliations:
Clinical Haematology,Alfred Health-Monash University,Melbourne,Australia
EHA Library. KALFF A. Jun 15, 2019; 267000; PS1383
Anna KALFF
Anna KALFF
Contributions
Abstract

Abstract: PS1383

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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 minimally pre-treated 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); and to evaluate the kinetics of response and loss of response (time to response [TTOR], time to disease progression [PFS], overall survival [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 RR MM (funded by the Victorian Cancer Agency, Australia). Key inclusion criteria were kappa-restricted myeloma, 1-3 prior lines of therapy but no prior LEN. In Stage 1 (n=30), patients received KappaMab (10mg/kg IV infusion) weekly for 8/52 (induction), then every 4/52 (maintenance). [One cycle = 28d]  For patients in Stage 2 (n=30), 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 was of 35 days duration: 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
40 patients have commenced therapy. Following review by the DMC, recruitment to Stage 1 was terminated early (n=19). 21 of a planned 40 patients for Stage 2 have commenced treatment.  Cut-off date for analysis: 15/2/2019.  13 patients remain on study (Stage 1=1, Stage 2=12). 19 have progressed (Stage 1=14, Stage 2=5), 6 withdrew consent (3 each stage), 1 other and 4 patients have died (Stage 1=2, Stage 2=2).

Observed CBR in Stage 1 was 5.3% (1/19, PR=1) compared to 66.7% in stage 2 (14/21, VGPR=2, PR=11, MR=1). (Response assessments are continuing and will be updated at the June meeting). Proof of concept (PoC) criteria were not met for Stage 1, but were met for Stage 2: observed CBR ≥ 55%, and the posterior probability (PP) that the true CBR exceeds 35% was > 0.95 (PP=0.998). ORR for Stage 1 was 5.3% (1/19) compared to 61.9% (13/21) for Stage 2. TTOR was not reached in Stage 1, and was 1.8m in Stage 2 (95% CI: 1.2 – 2.3m). Median PFS for stage 1 was 1.97m (95% CI: 1.67 - 4.63m), compared to 8.2m for patients in Stage 2 (95% CI 3.9 – 8.2m) (p=0.004).  Median OS for stage 1 was 16.4m (95% CI 4m and above), median OS for Stage 2 not reached (p=0.682).

AEs of interest: 3/19 patients in Stage 1 had infusion reactions (grade 1=1, grade 2=2), compared to 4/21 patients in Stage 2 (grade 2=4). There were no haematologic toxicities reported in Stage 1, in comparison to anaemia 2/21, neutropenia 3/21 (grade 3=3), thrombocytopenia 4/21 (grade 3=1, grade 4=2) reported in Stage 2.

Conclusion
PoC for efficacy was met for KappaMab when combined with LEN and DEX, and the combination is well tolerated. This novel IO combination may represent a promising new therapeutic option for MM patients. This study is ongoing.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Immunomodulatory thalidomide analog, Monoclonal antibody, Myeloma, Relapse

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