Evaluate the Safety, Tolerability, Biodistribution and Anti Tumour Activity of 177LU-OPS201 With Companion Imaging 68Ga-OPS202 PET/CT in Previously Treated Subjects With Locally Advanced or Metastatic Cancers Expressing Somatostatin Receptor 2 (SSTR2)

Study Overview
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Brief Summary
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This study consists of two phases. The phase I study is designed to investigate the safety and tolerability of Satoreotide tetraxetan following fractionated i.v. administrations in pre-treated subjects with locally advanced or metastatic cancers expressing sstr2 as identified by Satoreotide trizoxetan Positron Emission Tomography (PET/CT) scans. This phase will encompass both radioactivity escalation and peptide mass dose evaluation. Phase II will assess the efficacy of Satoreotide tetraxetan in subjects in selected indications, in a basket design.

Official Title
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A Multicentre, Open-Label Phase I/II Study to Evaluate the Safety, Tolerability, Biodistribution and Anti Tumour Activity of 177LU-OPS201 With Companion Imaging 68Ga OPS202 PET/CT in Previously Treated Subjects With Locally Advanced or Metastatic Cancers Expressing Somatostatin Receptor 2 (SSTR2)

Conditions
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Small Cell Lung Cancer and Breast Cancer

Intervention / Treatment
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* Drug: Satoreotide tetraxetan
* Drug: Satoreotide trizoxetan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consenting adults of Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Histologically confirmed locally advanced or metastatic disease which has progressed during or after, failed to respond to, or for which there is poor tolerability or after a contraindication to available Standard of Care (SoC) treatment options as per the assessment of the investigator; initially, subjects with the disease below may be considered: Subjects who had Extensive Disease (ED-SCLC) at presentation who have progressed on or after one line standard chemotherapy. If a subject had Limited Disease (LD-SCLC) at presentation and received surgery and/or radiotherapy as first line treatment (with or without chemotherapy) and has localized relapse, further local treatment (such as surgery) should be considered in addition to the chemotherapy options; For subjects with either ED-SCLC or LD-SCLC, if subjects relapse more than 6 months after first-line treatment, re-treatment with their initial regimen is recommended. Subjects may have received prior immunotherapy. Subjects with Human Epidermal Growth Factor Receptor (HR+)/(HER2-) metastatic BC after a failure of prior SoC-treatments and who have received, if indicated, at least one line of hormonal therapy, Cyclin-dependent kinase (CDK4/6) inhibitor and/or everolimus for advanced or metastatic disease and at least one line of chemotherapy for metastatic disease; subjects with a Breast Cancer (BRCA)-mutated metastatic disease who may have received a Poly adenosine diphosphate ribose polymerase (PARP) inhibitor, if available, are eligible; prior adjuvant hormonal treatment and prior adjuvant chemotherapy are allowed. Documented progressive disease (radiological, based on RECIST v1.1) within 3 months prior to first study drug administration. Screening study-related images should be sent to the Imaging core laboratory (ICL). Adequate organ function determined within 28 days prior to 177Lu-OPS201 administration, defined as follows: Haematological: white blood cells (WBC) ≥3000/μL, with absolute neutrophil count ≥1000/μL, platelet ≥100,000/μL and haemoglobin ≥9 g/dL (without a need for hematopoietic growth factor or transfusion support). Renal: Estimated glomerular filtration rate (eGFR) ≥55 mL/minute/1.73m2 Hepatic: total serum bilirubin ≤2×ULN; aspartate aminotransferase/ alanine aminotransferase ≤2.5×ULN (≤5×ULN if a subject has liver metastases) Formalin fixed paraffin embedded tumour sample (archival tumour sample obtained within 1 month prior to concent from the primary or metastatic lesion OR is willing to undergo newly obtained biopsy prior to the first dose of study treatment. Subjects who are unable or do not concent to provide acceptable tissue may not be enrolled unless there has been prior agreement with the sponsor. 68Ga OPS202 uptake in the target tissue (a primary tumour, lymph nodes longest diameter on PET/CT as confirmed by a central reader. Radiologically, ≥50% matching between the lesions detected on 68Ga OPS202-PET/CT and on 18F-fluorodeoxyglucose (18F-FDG)-PET/CT as confirmed by central reader Exclusion Criteria: Male subjects with BC. Unstable central nervous system metastasis Centrally located lung tumours that show radiogical evidence (CT or MRI) of either: cavitation or necrosis, or focal invasion for major blood vessels. Subjects had received chemotherapy within the previous 4 weeks or had not recovered from adverse events due to chemotherapy. Additional exclusion criteria were previous hemibody external radiotherapy, systemic radiotherapy with radioisotopes within the previous 24 weeks Previous chemotherapy within a cycle interval, curative radiotherapy within 4 weeks or palliative radiotherapy within 7 days prior to Investigational radiopharmaceutical product (IRPP) administration. Prior treatment with any other investigational medicinal product (IMP) within five half-lives of the previous IMP or within 2 weeks, if the previous compound is a mechanism-based molecularly targeted agent whose half-life is not well characterized and toxicities have not resolved from Grade 2 or higher prior to IRPP administration. Any unresolved NCI-CTCAE Grade 2 or higher toxicity (except alopecia and Grade 2 platinum-therapy related neuropathy) from previous antitumour treatment and/or medical/surgical procedures/interventions. Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject at high risk of renal toxicity during the study as assessed by the investigator. Any significant medical or surgical condition that would affect safety or the assessment of efficacy or the ability of a person to comply with the protocol. Any condition that precludes the proper performance of PET and/or SPECT scans, CT scans and/or MRI: subjects who are not able to tolerate the CT contrast agent. subjects with metal implants or joint prosthesis (depending on the location, if interferes with the PET and/or CT analysis) or any other objects that might interfere with the PET and/or CT analysis. subjects unable to raise arms for prolonged imaging purposes. subjects unable to lie still for the entire imaging time. subjects weighing greater than 130 kg (287 lb). Pregnant or lactating female. Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 6 months after the last dose of 177Lu-OPS201. Male subject who is unwilling to use acceptable method of effective contraception during treatment and through 6 months after the last dose of 177Lu-OPS201.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>i.v. administrations of up to three radioactivity levels of Satoreotide tetraxetan. | Drug: Satoreotide tetraxetan<br>* Radioactivity delivered in 2 administrations (cycles): one loading dose followed by a lower maintenance dose, 6 weeks apart until progression or unacceptable toxicity (up to 4 additional cycles could be administered depending on efficacy and tolerability).<br>* Other names: 177Lu-OPS201;Drug: Satoreotide trizoxetan<br>* Imaging companion: 1 administration at screening and one administration at End of core Trial cycle.<br>* Other names: 68Ga-OPS202;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Cumulative Activity - Phase I |  | From Day 1 (first administration of 177Lu-satoreotide tetraxetan) up to 6 weeks after the second administration; no longer applicable due to early study termination. | 
| Objective Response Rate Over the Two Treatment Cycles - Phase II |  | 6 weeks after each administration of 177Lu-satoreotide tetraxetan during the core study or at occurrence of first clinical signs of disease progression as determined by the investigator, up to 90 days; no longer applicable due to early study termination. |