A Phase 1 Prospective, Open-label, First-in-human Study to Evaluate the Safety, Tolerability and Biodistribution of [177Lu]Lu-AKIR001 and Its Anti-tumour Effect in Adult Patients With CD44v6 Expressing Solid Tumours

Karolinska University Hospital1 site in 1 country15 target enrollmentJanuary 28, 2026

ConditionsThyroid Gland Anaplastic Carcinoma Poorly Differentiated Thyroid Carcinoma Cancer Head and Neck Cervix Carcinoma Vulvar Cancer, Stage IV Non-small Cell Lung Cancer Stage IV

Interventions[177Lu]Lu-AKIR001

Overview

Phase: Early Phase 1
Intervention: [177Lu]Lu-AKIR001
Conditions: Thyroid Gland Anaplastic Carcinoma
Sponsor: Karolinska University Hospital
Enrollment: 15
Locations: 1
Primary Endpoint: Primary Endpoint - rate of dose limiting toxicities
Status: Recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

The goal of this clinical trial is to evaluate the safety and tolerability of increasing doses of [177Lu]Lu-AKIR001, both in relation to tolerable activity of lutetium-177 and the absorbed protein mass dose of AKIR-001 in patients with irresectable or metastatic CD44v6-expressing solid malignancies for whom no reasonable systemic treatment options are be available. The main question it aims to answer is:

• What is the toxicity profile of the study drug [177Lu]Lu-AKIR001 according to the rate of Dose Limiting Toxicities and (Severe) Adverse Events? Participants will receive one [177Lu]Lu-AKIR001 infusion followed by a 6-week safety follow-up period, which can be extended up to 12 weeks. Possible additional infusions of the trial drug, up to a maximum number of four, can be given when clinical benefit is noted and toxicity is deemed acceptable.

Registry

clinicaltrials.gov

Start Date

January 28, 2026

End Date

November 1, 2028

Last Updated

3 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Karolinska University Hospital

Responsible Party

Principal Investigator

Renske Altena

Associate Professor, MD PhD

Karolinska University Hospital

Eligibility Criteria

Inclusion Criteria

•Participant must be 18 years of age or older
•Willing and able to provide written informed consent
•Participant has one of the following histologically confirmed metastatic or locally advanced irresectable CD44v6 expressing (confirmed in pre-screening according to the pathology manual (Appendix III) solid malignancy in one of the following groups, with documented disease progression in the last 8 weeks during/after available standard of care treatment options as mentioned below:
•For anaplastic, poorly differentiated and radioiodine refractory differentiated thyroid cancer (ATC, PDTC, RAI-R DTC):
•For BRAFv600E mutated tumours: BRAF/MEK inhibitors.
•For BRAF-wildtype tumours at least one of the following: anthracycline- or taxane containing chemotherapy/ chemoradiotherapy, or other targeted therapies including vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI), targeted therapies aimed at specific moleculo-pathological features (e.g., targeting NTRK, RET, ALK, PD-L1)
•For PDTC or RAI-R DTC: Radio-iodine refractory disease as deemed by treating physician and disease progression after at least one line of systemic targeted therapy (including VEGF, TKI, NTRK, RET, BRAF inhibitors)
•For HNSCC:
•\- At least one prior treatment with combination chemotherapy (either platinum based + 5-Fluorouracil or platinum based + taxane) together with PD1-inhibitor pembrolizumab if combined positive score (CPS) ≥1 or EGFR-inhibitor if CPS \<1 (or if immunotherapy is contraindicated)
•For NSCLC

Exclusion Criteria

•Symptomatic brain metastases that are not previously treated and/or that require ongoing steroid-treatment
•Other malignancy diagnosed within the last five years, except for radically treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
•Chemo-, targeted or radiotherapy within the last 4 weeks before enrolment in the study.
•Ongoing toxicities graded according to the Common Terminology Criteria for Adverse Events (CTCAE) \> 1 from previous anti-cancer treatments.
•Pregnancy or lactation
•Uncontrolled hypertension, heart, liver, or kidney disease or other medical/ psychiatric disorders.
•Severe skin diseases requiring systemic anti-inflammatory treatment, including plaque psoriasis, Stevens Johnsons syndrome or dermatomyositis.
•A known history of Human Immunodeficiency Virus (HIV) infection, hepatitis B (HBsAg reactive) or hepatitis C (HCV RNA detected) infection or active tuberculosis.

Arms & Interventions

This is a single arm trial where patients are included in successive cohorts

In the successive cohorts, increasing doses of radioactivity (177-Lu) and CD44v6-targeted antibody (AKIR001) are given. A new dose cohort is opened only when toxicity in the previous dose cohort has deemed acceptable by the trial steering committee and the independent Data Safety Monitoring Board.

Intervention: [177Lu]Lu-AKIR001

Outcomes

Primary Outcomes

Primary Endpoint - rate of dose limiting toxicities

Time Frame: From first dose to a minimum of 6 weeks post-dose.

1. Rate of Dose Limiting Toxicities, according to the definition of (S)AEs according to the CTCAE version 5.0. 2. TEAEs, SAEs, clinically significant laboratory abnormalities and deaths 3. AEs ≥ grade 3 according to the CTCAE version 5.0 grading system (CTCAE v 5.0, 2017) during the treatment period