Clinical Trials /

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)

NCT03773133

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: D-FR-01072-002
  • NCT ID: NCT03773133

Conditions

  • Small Cell Lung Cancer and Breast Cancer

Interventions

DrugSynonymsArms
Satoreotide tetraxetan177Lu-OPS201Treatment
Satoreotide trizoxetan68Ga-OPS202Treatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentali.v. administrations of up to three radioactivity levels of Satoreotide tetraxetan.
  • Satoreotide tetraxetan
  • Satoreotide trizoxetan

Eligibility Criteria

        Inclusion Criteria:

          -  Consenting adults of Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or
             1

          -  Histologically confirmed locally advanced or metastatic disease that has progressed
             under or after, failed to respond to, or are intolerant or have 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:

               1. Subjects with Extensive Disease (ED-SCLC) that have progressed on or after
                  platinum-based chemotherapy or Limited Disease (LD-SCLC) that have progressed and
                  for which subject has exhausted standard treatment options; subjects may have
                  received prior immunotherapy.

               2. Subjects with Human Epidermal Growth Factor Receptor (HR+)/(HER2-) metastatic BC
                  after a failure of prior standard-of-care treatments and who have received, if
                  indicated, at least one line of hormonal therapy, Cyclin-dependent kinase
                  (CDK4/6) inhibitor 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. All images should be sent to the Imaging
             core laboratory (ICL).

          -  Adequate organ function determined within 21 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

               -  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
             21 days prior to the start of study treatment) 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 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 tumours with radiographic evidence (CT or MRI) of cavitary or
             necrotic lesions or focal invasion of major blood vessels.

          -  Previously received external beam irradiation to a field that includes more than 30%
             of the Bone marrow (BM).

          -  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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum administered cumulative activity (MTCA) - phase I
Time Frame:From Day 1 (first administration of 177Lu-OPS201) up to 6 weeks after the second administration.
Safety Issue:
Description:Determined as the incidence of Dose Limiting Toxicities (DLTs) and the cumulative organ absorbed doses (Gy) during two cycles of treatment. if the MTCA is not identified during the phase I, primary endpoint will be the Maximum administrable cumulative activity (MACA).

Secondary Outcome Measures

Measure:Maximum observed plasma drug concentration of 177Lu-OPS201 (Cmax) - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Time to maximum observed drug concentration of 177Lu-OPS201 (tmax) - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Maximal uptake (%) of 177Lu-OPS201 - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Area under the plasma concentration time curve (AUC) of 177Lu-OPS201 at the target lesions, discernible organs and blood - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Elimination half life (t1/2) of radioactivity concentrations in blood - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Highest absorbed dose to the target lesions (Gy/GBq) - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Specific absorbed dose per organ (Gy/GBq) - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Total plasma clearance (CL) - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Apparent volume of distribution (Vd) - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Cumulative amount (of unchanged drug) excreted into the urine (Ae) - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Renal clearance - phase I
Time Frame:Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days)
Safety Issue:
Description:
Measure:Mean change in tumour volume - phase II
Time Frame:46 weeks after each 177Lu-OPS201 administration compared to Screening as assessed by CT or MRI
Safety Issue:
Description:
Measure:Best overall response - phase I
Time Frame:Up to 24 months from the study start
Safety Issue:
Description:The best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for Pharmacodynamics (PD) the smallest measurements recorded since the treatment started)
Measure:Overall survival (OS)
Time Frame:At 1-year and 2-years follow-up from the study start
Safety Issue:
Description:
Measure:Quantitative changes in tumour
Time Frame:From Screening to 6 weeks after second 177Lu-OPS201 administration up to 90 days
Safety Issue:
Description:
Measure:Durable response rate (DRR) - phase II
Time Frame:From Screening and 6 weeks after each 177Lu-OPS201 administration up to 90 days
Safety Issue:
Description:DRR: Complete response (CR) or Partial response (PR) lasting ≥6 months
Measure:Progression free survival (PFS) - phase II
Time Frame:From Screening and 6 weeks after each 177Lu-OPS201 administration up to 90 days
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ipsen

Last Updated