[177Lu]Lu-AKIR001 First-in-human Study

NCT06639191 | Recruiting Early Phase 1 DMC

• 2 other identifiers: AKIR0012023-508126-95-00
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Radiopharmaceutical; first-in-human; CD44v6; Lutetium-177; 177Lu-AKIR001

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint - rate of dose limiting toxicities

  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

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

Secondary Outcomes (9)

• Biodistribution of 177Lu-AKIR001 in major organs and tissues

  8 days

• Biodistribution of 177Lu-AKIR001 in the whole body

  8 days

• Pharmacokinetics of 177-Lu and AKIR001 in major organs

  29 days

• Recommended Phase 2 Dose

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

• Anti-tumor efficacy: radiological response

  12 months

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: [177Lu]Lu-AKIR001

Interventions

[177Lu]Lu-AKIR001 DRUG

Patient cohorts of a minimum of three and a maximum of 12 evaluable participants will be opened according to the decision tree defined in the protocol and will be consecutively completed. When one cohort has been completed and fully evaluated, the next cohort will be opened after all participants in the previous cohort have received at least one dose of the IMP without dose-limiting toxicities during a follow-up period of at least six weeks. The \[177Lu\]Lu-AKIR001 protein mass dose and activity are predefined for each cohort, and could be adjusted according to the results of previous cohort(s) to ensure the safety of participants. The initial design of the trial encompasses five cohorts to escalate both \[177Lu\]Lu-AKIR001 pmd, from 50 mg to 100 mg, and activity, from 0.75 to 3.0 GBq.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• \- Treatment with at least two lines of systemic therapy, including checkpoint inhibitor based on PD-L1 status and chemotherapy with a platinum-based regimen.
• For vulvar SCC:
• \- After treatment with first line platinum/paclitaxel+/-bevacizumab +/- pembrolizumab (the latter in case of PD-L1 positivity), and second line with weekly paclitaxel
• For cervical SCC:
• After treatment with first line systemic therapy with platinum/paclitaxel+/-pembrolizumab (the latter in case of PD-L1 positivity)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karolinska University Hospital: lead
• Karolinska Institutet: collaborator
• Uppsala University: collaborator

Study Sites (1)

Karolinska University hospital

Stockholm, Stockholm County, 17176, Sweden

RECRUITING

Related Publications (1)

• Mortensen ACL, Mohajershojai T, Gustafsson A, Berglund H, Selvaraju RK, Hofstrom C, Persson H, Ohlin M, Tran TA, Moren AF, Ochniewicz P, Zedenius J, Bernhardt P, Frejd FY, Nestor M. Preclinical Validation of [177Lu]Lu-AKIR001, a CD44v6-Targeted Radiotherapeutic Entering First-in-Human Trials. J Nucl Med. 2026 Feb 2;67(2):269-275. doi: 10.2967/jnumed.125.270782.

  PMID: 41198237 DERIVED

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic; Head and Neck Neoplasms; Uterine Cervical Neoplasms; Vulvar Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Vulvar Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Renske Altena, Associate Professor, MD PhD

CONTACT

+46812375518; renske.altena@ki.se

Thuy Tran, Associate Prof, PharmD, PhD

CONTACT

+46727418988; thuy.tran@ki.se

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, MD PhD

Model Details: This is a prospective, open-label, first-in-human Phase 1 dose-finding trial. Patients will be included in consective dosing cohorts, with both increasing doses of radioactivitity (Lutetium-177) and the CD44v6-targeted antibody (AKIR001)

Study Record Dates

• First Submitted: October 8, 2024
• First Posted: October 15, 2024
• Study Start: January 28, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

SE (1)