FDA Clears IND of Off-the-Shelf In Vivo CAR-T Therapy for R/R Myeloma

The FDA has granted clearance to the investigational new drug (IND) application for KLN-1010, a novel off-the-shelf in vivo gene therapy, for the treatment of patients with relapsed/refractory (R/R) multiple myeloma.¹

This decision follows a recent presentation of first-in-human data at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2025. These data, derived from the ongoing phase 1 inMMyCAR trial (NCT07075185) in Australia, provided evidence of early clinical activity and manageable safety in the first 4 patients dosed with KLN-1010.²

The FDA’s IND clearance marks a key step forward in the development of KLN-1010, enabling expansion of the phase 1 study to multiple sites in the US.

"This IND clearance is an important milestone for KLN-1010 and for the broader field of in vivo CAR-T therapy," said Kevin Friedman, PhD, CEO of Kelonia Therapeutics, in a news release.¹ "Last month, we presented initial safety and efficacy data from the first [4] patients treated in our [p]hase 1 study, all of whom achieved MRD-negative responses at [1] month, with durability extending through [3] months in the patients with the longest follow-up. The FDA’s clearance allows us to accelerate enrollment across multiple geographies and brings us a meaningful step closer to our goal of democratizing CAR-T therapies for patients with multiple myeloma."

About KLN-1010: Overcoming CAR T Limitations

Although chimeric antigen receptor T (CAR-T) cell therapies have revolutionized the treatment landscape for hematologic malignancies, several practical limitations and barriers to patient access remain. These limitations include specific manufacturing processes, therapy administration complexities, and the requirement of lymphodepleting preconditioning chemotherapy prior to infusion.

KLN-1010 is an intravenously administered gene therapy that works by generating anti-B cell maturation antigen (BCMA) CAR-T cells targeting the surfaces of myeloma cells. Unlike conventional CAR-T cell therapies, KLN-1010’s approach introduces a single-infusion, in vivo CAR-T platform that does not require prior chemotherapy or ex vivo cell manufacturing. The off-the-shelf agent is designed to be readily available, potentially eliminating long wait times and facilitating broader access to CAR-T cell therapies.

By addressing key limitations of current CAR-T treatments, the therapy has the potential to meaningfully expand the role of CAR-T therapy in multiple myeloma.

Trial Design and Clinical Data

The objective of the phase 1 dose-escalation and -expansion study is to evaluate the safety, tolerability, and preliminary efficacy of KLN-1010 and to determine the recommended phase 2 dose in patients with R/R myeloma.³ Currently open for enrollment across 3 sites in Australia, the study intends to enroll an estimated total of 40 patients. For inclusion, patients must have received at least 3 prior lines of therapy including a proteasome inhibitor, immunomodulatory drug, and a CD38-directed monoclonal antibody.

Preliminary findings presented at the ASH meeting revealed that clinical responses per International Myeloma Working Group (IMWG) criteria appeared to deepen over time with KLN-1010, with all patients experiencing minimal residual disease (MRD)-negative responses at month 1 that were sustained through month 3 and beyond.²

Additionally, the findings indicated measurable T-cell expansion, even in the absence of lymphodepleting chemotherapy. CAR-positive T cells were detected in the blood on day 15. CAR-T cells, predominantly memory-phenotype T cells, were also detected in the bone marrow and peripheral blood through the third month, suggesting durable immune responses.

Regarding safety, the therapy demonstrated a manageable adverse event (AE) profile, with events occurring primarily around infusion and during CAR-T expansion. Treatment-emergent AEs included infusion-related reactions (IRRs; n = 2), both of which resolved within 6 to 48 hours, as well as lymphocytosis, hypomagnesemia, and hypokalemia. Grade 3 or higher treatment-emergent AEs included febrile neutropenia, IRRs, lymphopenia, lymphocytosis, anemia, vasovagal syncope, and pneumonia (n = 1 each). Two patients experienced grade 2 cytokine release syndrome. Cytopenias were minimal, with 1 patient having grade 3 anemia and 1 patient having grade 3/4 neutropenia.

REFERENCES

1. Kelonia Therapeutics announces FDA clearance of investigational new drug (IND) application for KLN-1010, an in vivo BCMA CAR-T therapy for relapsed and refractory multiple myeloma. News release. Kelonia Therapeutics. January 7, 2026. Accessed January 7, 2026. https://tinyurl.com/23hdt9xf

2. Harrison S, Ho PJ, Lim SL, et al. Minimal residual disease (MRD)-negative outcomes following a novel, in vivo gene therapy generating anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells in patients with relapsed and refractory multiple myeloma (RRMM): Preliminary results from inMMyCAR, the first-in-human phase 1 study of KLN-1010. Blood. 2025;146(Supplement 2):LBA-1. doi:10.1182/blood-2025-lba-1

3. A study to evaluate a novel gene therapy in patients with relapsed and refractory multiple myeloma (inMMyCAR). ClinicalTrials.gov. Updated September 2, 2025. Accessed January 7, 2026. https://clinicaltrials.gov/study/NCT07075185