In Vivo CAR T Takes Center Stage, With Results Shared for 3 MRD-Negative Patients

This morning, care for multiple myeloma—and all of cancer—will take a major turn when an Australian scientist describes an infusion that generates a novel treatment inside the body, bypassing a process that can take weeks while cancer rages.

In vivo chimeric antigen receptor (CAR) T-cell therapy is here—sooner than expected—and today, it kicks off the late-breaking session at the 67th American Society of Hematology Annual Meeting & Exposition.¹ Never mind that only 112 days have passed since the announcement that presenter Phoebe Joy Ho, MBBS, DPhil, professor at the University of Sydney, dosed the first patient with KLN-1010,² the investigational treatment from Kelonia Therapeutics,³ one of the dozens of players large and small in a billion-dollar quest4^,5 to deliver the next generation of one-and-done cancer treatments.

If successful, in vivo CAR T-cell therapy could overcome barriers that put today’s CAR T-cell therapies beyond the reach of many patients: a time-consuming manufacturing process that is expensive and gives cancer time to progress, and a need to stay in the hospital or immediately nearby when the therapy is given, due to fears of adverse events (AEs).

For years, there have been reports of both progress and setbacks in “off the shelf” CAR T-cell therapy, but much of this has surrounded allogeneic solutions—those that would involve donor cells, perhaps modified with gene editing. Besides eliminating the wait time, some believe these treatments could be produced at a dramatically lower cost per dose—perhaps 5 figures vs the 6-figure sums for CAR T-cell therapy. However, the concern has been that patients would risk the possibility of graft-vs-host disease.

In vivo therapy addresses this problem, Michael Rosenzweig, MD, MS, chief, Division of Multiple Myeloma, City of Hope, said in an interview with The American Journal of Managed Care^®. “With the in vivo technology, patients would not be exposed to a foreign molecule. It's an internal molecule that's made by the patient themselves. And so, the risks of adverse reactions would presumably be lower,” he said.

As reported by Evidence-Based Oncology™ in August,⁴ there are 2 basic in vivo technologies under development: viral vectors and lipid nanoparticles, which use a delivery platform similar to messenger RNA (mRNA) COVID-19 vaccines. Both eliminate the need to collect T cells from patients, along with subsequent manufacturing and hospital stays.

Kelonia Therapeutics uses a version of the first technology. In their abstract, the authors say the gene therapy generates anti-BCMA CAR T cells, and that “selective transduction of circulating T cells is achieved through an improved third-generation lentiviral vector (LVV), comprised of a modified vesicular stomatitis virus glycoprotein fusogen coexpressed with an anti-CD3 antibody on the LVV envelope." This enables viral entry through CD3 on T cells, “rather than the low-density lipoprotein receptor.”

The authors call their treatment “an off-the-shelf therapy” that “eliminates the need for apheresis, bespoke ex vivo cell manufacturing, or lymphodepleting chemotherapy.” KLN-1010, they write, “may broaden access to CAR-T therapies.”

The phase 1 trial, called inMMyCAR (NCT07075185), is designed to evaluate the safety and tolerability of the therapy and develop a recommended phase 2 dose of KLN-1010 in patients with relapsed or refractory (R/R) multiple myeloma. According to information filed with FDA, the phase 1 study seeks to enroll 40 patients. Patients must have R/R multiple myeloma with measurable disease, adequate end-organ and bone marrow function, and at least 3 prior lines of therapy, including a proteosome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody.

Kelonia surprised many with its November 24, 2025, announcement that it would present data from 3 patients dosed with KLN-1010 during ASH’s late-breaking session.³ Several analysts said the small number of patients means that no one should react too strongly to the news, especially after stocks dipped for some companies developing allogeneic CAR T-cell therapeutics.

Rosenzweig agreed that balancing the high level of interest with caution is in order. “It’s very early. They’re only reporting on 3 patients, so we still have a lot more to learn,” he said. “But it’s definitely an exciting abstract that's beginning, at least, to offer proof of principle that it’s possible to do this with some efficacy.”

A major outstanding question is whether the therapy is durable, Rosenzweig said. “How long are those CAR T cells that are being made in vivo going to persist and provide excellent disease control?” he asked. “In the first 3 patients, we're seeing great responses early… But how durable are those responses, and how durable are the lack of adverse events? Will we see delayed toxicity, delayed neurotoxicity, or any kind of delayed adverse events?"

A Highly Competitive Landscape

Companies that have joined the in novo race include the original CAR T players: Novartis, which is working with Vyriad, and Gilead, which acquired Interius BioTherapeutics. Other major pharma companies in the mix include AstraZeneca, which acquired EsoBiotec, and AbbVie, which acquired Capstan Therapeutics and has licensing agreements for Umoja Biopharma projects. Capstan’s mRNA lipid nanoparticle approach is similar to what competitors Orna Therapeutics and Myeloid Therapeutics are using. Kelonia’s competitors on the viral vector side include Umoja and Interius,

When the ZUMA-1 trial for axicabtagene ciloleucel (axi-cel/Yescarta; Kite/Gilead) was presented at ASH in December 2016, attendees were wowed by results that showed 76% of patients with diffuse-large B-cell lymphoma (DLBCL) had an objective response after not responding to the last 2 lines of therapy. These were patients who had run out of options. But the good news was offset by reports of significant adverse events, including cytokine release syndrome (CRS). What’s more, making this therapy required harvesting the patient’s T cells and engineering them to find cancer in a process that could take 6 weeks. For some with an aggressive cancer such as DLBCL, CAR T-cell therapy was not an option.

“KLN-1010 is beginning to show the extraordinary clinical outcomes that may be possible with in vivo CAR-T therapy — early, deep responses from a single infusion without the barriers that limit access to traditional CAR-T treatments,” Kevin Friedman, PhD, CEO and Kelonia cofounder, said in a statement when the late-breaker status was announced.³ “We are encouraged by these first-in-human results and looking forward to sharing additional details from the study with the scientific and medical communities….”

Kelonia is expected to offer updated data this morning during this morning’s late-breaking session.

Authors described the study design as 3+3 dose escalation with half-log dose increments. Results are as follows¹:

• The 3 patients range in age from 61 to 72 years, and their time from diagnosis was 7.9 to 9.4 years. All had high-risk cytogenetics and 3 to 4 prior lines of therapy.
• Time from consent to infusion was 13 to 18 days. No lymphodepletion was required.
• Two were refractory to a PI, an IMiD, and anti-CD38 therapy. All were naïve to BCMA-targeted therapies.
• All 3 patients experienced treatment-emergent AEs, primarily around infusion and during CAR T expansion. Two patients developed infusion-related reactions 30 to 60 minutes post-infusion that resolved within 6 to 48 hours.
• Tocilizumab was administered prophylactically in the latter 2 patients during CAR T expansion.
• No immune effector cell-associated neurotoxicity syndrome (ICANS) or delayed neurotoxicity, such as parkinsonism or cranial nerve palsies were observed.
• One patient had grade 3 anemia lasting 1 day (day 15); 1 patient had grade 3/4 neutropenia on days 1 and 15.
• No cases of grade 3 or higher thrombocytopenia, hematologic toxicity, or treatment-emergent infections at 1 month.
• MRD-negative responses (10^-5 or 10^-6 sensitivity) were seen in all patients at the 1-month mark, with the patient treated first maintaining MRD-negativity (10^-6) at month 3.
• No clinical sequelae of the lymphocytosis were noted; dexamethasone promptly resolved the lymphocytosis in the patient with the highest absolute lymphocyte count. CAR T cells were detected in the bone marrow and peripheral blood through month 3; these were mostly memory-phenotype T cells.

The authors reported that all patients had achieved a partial response at month 1 by IMWG criteria and that responses deepened over time; the best response was a very good partial response (VGPR) at month 3. Responses continue without disease progression.

“KLN-1010 demonstrates that promising clinical activity and manageable toxicities are feasible with an off-the-shelf in vivo CAR-T in MM,” the authors concluded.¹

References

1. Ho PJ, Harrison S, Talam S, 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. Presented at: 67^th American Society of Hematology Annual Meeting & Exposition, December 6-9, 2025; Orlando, FL. Abstract LBA-1.
2. Kelonia Therapeutics doses first patient in phase 1 inMMyCAR study evaluating in vivo CAR T-cell therapy for relapsed and refractory multiple myeloma. News release. Kelonia Therapeutics. August 19, 2025. Accessed December 8, 2025. https://keloniatx.com/kelonia-therapeutics-doses-first-patient-in-phase-1-inmmycar-study-evaluating-in-vivo-car-t-cell-therapy-for-relapsed-and-refractory-multiple-myeloma/
3. Kelonia Therapeutics announces late-breaking oral presentation of first-in-human data from in vivo BCMA CAR T therapy at the American Society of Hematology (ASH) 2025 annual meeting. News meeting. Kelonia Therapeutics. November 24, 2025. Accessed December 8, 2025. https://keloniatx.com/kelonia-therapeutics-announces-late-breaking-oral-presentation-of-first-in-human-data-from-in-vivo-bcma-car-t-therapy-at-the-american-society-of-hematology-ash-2025-annual-meeting/
4. Flinn R. How in vivo CAR T-cell therapies could rewrite the cancer care playbook. Am J Manag Care. 2025;31(Spec 9):SP574-SP576
5. Dolgin E. In vivo CAR T Sparks Billion-Dollar Race. Cancer Discov News. AACR. September 9, 2025. doi:10.1158/2159-8290.CD-NW2025-0072