Swedish biotechnology company Akiram Therapeutics has released the first clinical findings from its ongoing Phase 1 trial of lutetium-177 AKIR001, an antibody-based radiopharmaceutical being developed for patients with advanced solid tumors who have exhausted standard treatment options. Eight patients had received treatment at the data cutoff, with no dose-limiting toxicities reported and treatment-related adverse events limited to grades 1 and 2. Four patients received additional treatment following their initial administration, supporting continued investigation of repeat dosing.
The first-in-human study (NCT06639191) is being conducted at Karolinska University Hospital in Stockholm and is evaluating the safety, tolerability and pharmacokinetics of AKIR001 in patients with unresectable or metastatic CD44v6-positive solid tumors. The preliminary findings will be presented Oct. 18 at the European Association of Nuclear Medicine Congress in Vienna, where the clinical study has been selected for a top-rated oral presentation.
AKIR001 combines Lu-177 with a proprietary antibody that targets CD44v6, a variant of the CD44 cell-surface protein associated with several solid tumor types. The approach is designed to deliver therapeutic radiation to cancer cells expressing the marker while limiting radiation exposure to surrounding healthy tissue. Potential applications include lung, head and neck, thyroid and gynecological cancers, although the treatment remains in early clinical development.
Quantitative imaging from the first eight patients showed sustained retention of the radiopharmaceutical in tumor tissue, accompanied by clearance from blood and normal tissues. These findings are important for an antibody-based radiopharmaceutical, where the time required for the targeting molecule to accumulate in tumors and clear from healthy organs can influence both radiation exposure and treatment tolerability.
The ability to administer repeat treatment is another consideration as Akiram advances through dose escalation. Although the company has not disclosed detailed tumor response measurements, the absence of dose-limiting toxicities at the activity levels evaluated so far supports continued investigation of higher administered activities.
"We are encouraged by the safety profile and sustained tumor retention observed so far," said Marika Nestor, CEO of Akiram Therapeutics. She also pointed to the ability to administer repeat treatment as an encouraging finding for the program.
The initial results are based on a small patient population and are primarily intended to assess safety and how the radiopharmaceutical behaves in the body. Additional patients and longer follow-up will be needed to determine whether the observed tumor retention translates into meaningful clinical responses and whether toxicity changes at higher activity levels.
The study also identified a relationship between CD44v6 expression and radiation absorbed by tumors. Patients whose tumors showed low levels of the target protein on immunohistochemistry testing consistently received lower absorbed tumor doses, suggesting that target expression may influence how effectively AKIR001 delivers radiation.
That relationship could become useful in determining which patients are most appropriate for treatment. Immunohistochemistry, which evaluates protein expression in tissue samples, could potentially provide a screening method for identifying tumors with sufficient CD44v6 expression before administering the radiopharmaceutical. The findings remain preliminary, and the company has not established a validated expression threshold for patient selection.
CD44v6 has attracted interest as a therapeutic target because it is expressed across several malignancies rather than being limited to a single cancer type. Akiram is investigating whether its antibody-based approach can support treatment across different CD44v6-positive tumors, potentially allowing the same radiopharmaceutical to be developed for multiple indications.
The company has also been evaluating the underlying targeting platform in preclinical models. Research published in The Journal of Nuclear Medicine earlier this year demonstrated selective tumor uptake and antitumor activity in several experimental models, helping support the transition into human testing.
Akiram's clinical program is supported by a supply agreement with ITM Isotope Technologies Munich, which agreed in August to provide non-carrier-added Lu-177 for AKIR001 development. The arrangement gives Akiram access to the therapeutic radionuclide as it advances the dose-escalation study and evaluates future clinical development requirements.
The company is also investigating whether different antibody formats could expand the use of its CD44v6-targeting platform. A separate preclinical study scheduled for presentation at EANM on Oct. 20 evaluates AKIR001 and a smaller single-chain variable fragment antibody format for potential theranostic applications in bladder cancer. The work examines an additional tumor type and a different targeting approach, although it has not yet progressed to clinical testing.
The ongoing Phase 1 trial has already advanced through several dose-escalation cohorts, including progression to cohort 3 earlier this year following a safety review. Investigators are continuing to assess the relationship between administered activity, tumor uptake and normal-tissue exposure as treatment levels increase.
The complete clinical presentation at EANM is expected to provide additional information about the eight treated patients, including the activity levels investigated and findings from dosimetry and safety assessments. Akiram has not announced a timetable for completing the Phase 1 study or advancing AKIR001 into later-stage clinical trials.
