Novel CAR T Targeting Kappa Myeloma Antigen Enters First-in-Human Trial

A novel autologous chimeric antigen receptor (CAR) T-cell approach targeting the Kappa Myeloma Antigen (KMA) is now being investigated in patients with relapsed or refractory kappa-restricted multiple myeloma, according to a news release from HaemaLogiX Ltd.¹

The first-in-human phase 1 KOALA study (NCT07541391) of KMCAR T-cell therapy is now open to enrollment at Australia’s Peter MacCallum Cancer Centre (Peter Mac), following receipt of clinical trial approval from Australia’s Therapeutic Goods Administration and institutional ethics approval.

Rationale and Mechanism

Despite the introduction of B-cell maturation antigen (BCMA)–directed CAR T-cell therapies, most patients are at risk of eventual relapse, and currently approved agents carry the risk of depleting normal immunoglobulin-producing plasma cells, leaving patients vulnerable to serious infections such as pneumonia.

KMCAR T-cell therapy takes a mechanistically distinct approach; rather than targeting BCMA, which is expressed on both malignant and normal plasma cells, KMCAR T cells are engineered to recognize KMA, a tumor-specific antigen found exclusively on myeloma cells and not present in healthy immune cells. This selectivity is designed to achieve targeted tumor cytotoxicity while preserving normal immune function, an important differentiation from approved BCMA-directed products in a patient population already at elevated infectious risk.

Patients must undergo apheresis to remove the T cells that are then modified to express a chimeric antigen receptor directed against KMA and reinfused. The CAR T construct is derived from HaemaLogiX’s proprietary KappaMab antibody platform, which has been evaluated across multiple phase 1, 2a, and 2b clinical trials and has demonstrated a favorable safety profile and durable responses in studies of the KappaMab (MDX-1097) monoclonal antibody.² Preclinical work conducted jointly by HaemaLogiX and Peter Mac showed specific and durable killing of KMA-positive tumor cells, providing proof-of-concept for the CAR T modality.¹

Trial Design and Setting

The KOALA study is a single-center phase 1 dose-escalation trial with dual objectives of assessing safety and generating preliminary efficacy data in patients with relapsed or refractory kappa-restricted multiple myeloma. Cell manufacturing is being performed by Cell Therapies Pty Ltd, a TGA-licensed Good Manufacturing Practice facility partnered with Peter Mac, which could support a seamless transition to a potential phase 1b expansion and future development, according to the company.

There is an estimated enrollment of 12 patients with primary completion of the study estimated in September of 2028.³ Patients must have a diagnosis of kappa-restricted multiple myeloma with evidence of KMA on the surface of bone marrow plasma cells. They must have received at least 2 prior lines of therapy including a proteasome inhibitor and immunomodulatory drug, and may have received prior CAR T-cell therapy after a washout period of 12 weeks between infusions. Other eligibility criteria include ECOG performance status of 0 to 2 and adequate cardiac, hepatic, pulmonary, and renal function.

“This milestone reflects years of scientific collaboration and commitment to developing a targeted, tumor-specific approach for patients with relapsed or refractory multiple myeloma,” said Rosanne Dunn, PhD, MSc, chief scientific officer and co-founder of HaemaLogiX, in the news release. “We are excited to see our KMCAR T-cell therapy progress into clinical testing and look forward to the insights the KOALA study will generate.”

REFERENCES

1. KOALA trial reaches major milestone with commencement of patient enrolment. News release. HaemaLogiX. May 19, 2026. Accessed May 20, 2026. https://tinyurl.com/mpdm8azp

2. Spencer A, Kalff A, Shortt J, et al. A sequential cohort study evaluating single-agent KappaMab and KappaMab combined with lenalidomide and low-dose dexamethasone in relapsed and/or refractory kappa light chain-restricted multiple myeloma (AMaRC 01-16). Br J Haematol. 2023;202(4):801-811. doi:10.1111/bjh.18955

3. Autologous Chimeric Antigen Receptor (CAR) T-cells Targeting the Kappa Myeloma Antigen (KMA) in Kappa Restricted Multiple Myeloma Patients With Relapsed/​Refractory Disease (KOALA). ClinicalTrials.gov. Updated April 30, 2026. Accessed May 20, 2026. https://clinicaltrials.gov/study/NCT07541391