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

Required: CD44 v6 expressing

CD44v6 expressing (confirmed in pre-screening according to the pathology manual (Appendix III))

Allowed: BRAF V600E

For BRAFv600E mutated tumours: BRAF/MEK inhibitors

Allowed: BRAF wild-type

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)

Must have received: BRAF inhibitor — BRAF V600E mutated ATC/PDTC/RAI-R DTC

For BRAFv600E mutated tumours: BRAF/MEK inhibitors

Must have received: MEK inhibitor — BRAF V600E mutated ATC/PDTC/RAI-R DTC

For BRAFv600E mutated tumours: BRAF/MEK inhibitors

Must have received: anthracycline — BRAF-wildtype ATC/PDTC/RAI-R DTC

For BRAF-wildtype tumours at least one of the following: anthracycline- or taxane containing chemotherapy/ chemoradiotherapy

Must have received: taxane — BRAF-wildtype ATC/PDTC/RAI-R DTC

For BRAF-wildtype tumours at least one of the following: anthracycline- or taxane containing chemotherapy/ chemoradiotherapy

Must have received: VEGFR inhibitor — BRAF-wildtype ATC/PDTC/RAI-R DTC

other targeted therapies including vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI)

Must have received: targeted therapy — BRAF-wildtype ATC/PDTC/RAI-R DTC

targeted therapies aimed at specific moleculo-pathological features (e.g., targeting NTRK, RET, ALK, PD-L1)

Must have received: radioiodine — 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)

Must have received: systemic targeted therapy — PDTC or RAI-R DTC

disease progression after at least one line of systemic targeted therapy (including VEGF, TKI, NTRK, RET, BRAF inhibitors)

Must have received: platinum-based chemotherapy — HNSCC

combination chemotherapy (either platinum based + 5-Fluorouracil or platinum based + taxane)

Must have received: antimetabolite (5-Fluorouracil) — HNSCC

combination chemotherapy (either platinum based + 5-Fluorouracil or platinum based + taxane)

Must have received: taxane — HNSCC

combination chemotherapy (either platinum based + 5-Fluorouracil or platinum based + taxane)

Must have received: anti-PD-1 therapy (pembrolizumab) — HNSCC, CPS ≥1

PD1-inhibitor pembrolizumab if combined positive score (CPS) ≥1

Must have received: EGFR inhibitor — HNSCC, CPS <1 or if immunotherapy is contraindicated

EGFR-inhibitor if CPS <1 (or if immunotherapy is contraindicated)

Must have received: checkpoint inhibitor — NSCLC

checkpoint inhibitor based on PD-L1 status

Must have received: platinum-based chemotherapy — NSCLC

chemotherapy with a platinum-based regimen

Must have received: platinum-based chemotherapy — vulvar SCC, first line

first line platinum/paclitaxel+/-bevacizumab +/- pembrolizumab (the latter in case of PD-L1 positivity)

Must have received: taxane (paclitaxel) — vulvar SCC, first line

first line platinum/paclitaxel+/-bevacizumab +/- pembrolizumab (the latter in case of PD-L1 positivity)

Must have received: VEGF inhibitor (bevacizumab) — vulvar SCC, first line

first line platinum/paclitaxel+/-bevacizumab +/- pembrolizumab (the latter in case of PD-L1 positivity)

Must have received: anti-PD-1 therapy (pembrolizumab) — vulvar SCC, first line, in case of PD-L1 positivity

first line platinum/paclitaxel+/-bevacizumab +/- pembrolizumab (the latter in case of PD-L1 positivity)

Must have received: taxane (paclitaxel) — vulvar SCC, second line

second line with weekly paclitaxel

Must have received: platinum-based chemotherapy — cervical SCC, first line

first line systemic therapy with platinum/paclitaxel+/-pembrolizumab (the latter in case of PD-L1 positivity)

Must have received: taxane (paclitaxel) — cervical SCC, first line

first line systemic therapy with platinum/paclitaxel+/-pembrolizumab (the latter in case of PD-L1 positivity)

Must have received: anti-PD-1 therapy (pembrolizumab) — cervical SCC, first line, in case of PD-L1 positivity

first line systemic therapy with platinum/paclitaxel+/-pembrolizumab (the latter in case of PD-L1 positivity)

Cannot have received: chemotherapy

Chemo-, targeted or radiotherapy within the last 4 weeks before enrolment in the study.

Cannot have received: targeted therapy

Chemo-, targeted or radiotherapy within the last 4 weeks before enrolment in the study.

Cannot have received: radiation therapy

Chemo-, targeted or radiotherapy within the last 4 weeks before enrolment in the study.