Study to Evaluate the Safety and Preliminary Efficacy of 177Lu-OPS201 in NETs

• Register: ClinicalTrials.gov
• Last refreshed on: 2 August 2023
• Main ID: NCT02592707
• Date of registration: 15/10/2015
• Prospective Registration: Yes
• Primary sponsor: Ipsen
• Public title: Study to Evaluate the Safety and Preliminary Efficacy of 177Lu-OPS201 in NETs
• Scientific title: An International, Multicenter, Open-label Study to Evaluate Safety, Tolerability, Biodistribution, Dosimetry and Preliminary Efficacy of 177Lu-OPS201 for the Therapy of Somatostatin Receptor-positive Neuroendocrine Tumors (NETs)
• Date of first enrolment: March 6, 2017
• Target sample size: 40
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT02592707
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Austria, Canada, Denmark, France, Switzerland, United Kingdom, United States

Contacts

• Name: Ipsen Medical Director
• Affiliation: Ipsen

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Written informed consent.

2. Patients of either gender, aged = 18 years.

3. Women of childbearing potential (not surgically sterile or less than 2 years
postmenopausal) must use a medically accepted method of contraception and must agree
to continue use of this method for the duration of the study and for 6 months after
the last dose. Acceptable methods of contraception include abstinence, or double
contraception: steroidal contraceptive (oral, transdermal, implanted, and injected) in
conjunction with a barrier method (intrauterine device, condom etc.).

4. Male patients must use a medically accepted method of contraception and must agree to
continue use of this method for the duration of the study and for 6 months after the
last activity administration.

5. Karnofsky performance score = 60.

6. Life expectancy of at least 6 months.

7. Histologically confirmed diagnosis of -

- unresectable GEP NET (Grade I and Grade II according to WHO classification (2010,
Annex 01), functioning and non-functioning).

- unresectable "typical lung carcinoid" or "atypical lung carcinoid" are acceptable
(with the exception of Large Cell Bronchial Neuroendocrine Neoplasms and Small
Cell Lung Cancers) (Caplin 2015).

- malignant, unresectable pheochromocytoma or paraganglioma

8. Documentation of progressive disease based on RECIST v1.1 under prior anti-tumor
therapy within 6 months of entry in the study (although the progression might have
occurred more than 6 months before study entry). Patients should not have received
further anti-tumor therapy once disease progression is documented. The images of this
evaluation should be available for TGR evaluation.

9. In countries where sunitinib or everolimus are marketed, patients with GEP NET and
lung NET will be progressive under this prior anti-tumor treatment for the respective
indication. Patients not suitable for everolimus/sunitinib therapy according to a
tumor board decision (or comparable local practice) may also be enrolled into the
study. Patients having everolimus/sunitinib therapy should have a wash-out phase of =
4 weeks before the first treatment.

10. Measurable disease based on RECIST v1.1.

11. Confirmed presence of somatostatin receptors on technically evaluable tumor lesions
documented by a positive Somatostatin Receptor Scan performed within 6 months prior to
enrolment in the study.

12. Calculated GFR = 55 mL/min.

13. Blood test results as follows:

- Leukocytes: = 4*10^9/L

- Erythrocytes: = 3.5*12^9/L

- Platelets: = 100*10^9/L

- Albumin: > 30 g/L

- ALT, AST, AP: = 5 times ULN (upper limit of normal)

- Bilirubin: = 2 times ULN (2x 1.1 mg/dL)

Exclusion Criteria:

1. Known hypersensitivity to 177Lu, to DOTA, to JR11 or to any of the excipients of
177Lu-OPS201.

2. Any previous peptide receptor radionuclide therapy (PRRT).

3. Diagnosis of thymic NET.

4. Presence of active infection at screening or history of serious infection within the
previous 6 weeks.

5. Administration of any other investigational medicinal product within 60 days prior to
entry.

6. Prior or planned administration of a therapeutic radiopharmaceutical within 8
half-lives of the radionuclide including any time during the current study.

7. Any extensive radiotherapy = 3 months before enrolment.

8. Chemotherapy = 3 months before enrolment.

9. Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject
at high risk of renal toxicity during the study as assessed by the investigator.

10. Pregnant or breast-feeding women: A pregnancy test will be performed at the start of
the study for all female patients of childbearing potential (i.e. not surgically
sterile or up to 2 years postmenopausal).

11. Any uncontrolled significant medical, psychiatric or surgical condition (active
infection, unstable angina pectoris, cardiac arrhythmia, poorly controlled
hypertension, poorly controlled diabetes mellitus [HbA1c =9%], uncontrolled congestive
heart disease, etc.) or laboratory findings that, in the opinion of the investigator,
might jeopardize the patient's safety or that would limit compliance with the
objectives and assessments of the study. Note: the patient should be able to tolerate
high volume load.

12. Current history of any malignancy other than NET within 5 years of enrolment except
for fully -resected non-melanoma skin cancer or cervical cancer in situ. Current
history of malignancy; patients with a secondary tumor in remission of > 5 years can
be included

13. Any mental condition rendering the patient unable to understand the nature, scope and
possible consequences of the study, and/or evidence of an uncooperative attitude.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Neuroendocrine Tumors

Intervention(s)

Other: Antiemetic

Drug: Satoreotide tetraxetan

Other: Amino acid solution

Primary Outcome(s)

Number of Participants With Dose Limiting Toxicities (DLT) [Time Frame: From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks.]

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs [Time Frame: From the start of the first study medication (Cycle 1 Day 1) up to 6 months after the last dose of study medication, maximum of 33 months]

Secondary Outcome(s)

Change From Baseline in QLQ Gastro-intestinal. Neuroendocrine Tumour (GI.NET)21 at EOCT Visit [Time Frame: Baseline (Day 1) and EOCT visit (30 months)]

Fraction of IPN01072 Excreted Into the Urine (Fe) in Cycle 1 [Time Frame: 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 in Part B]

Ae (0-48h) of IPN01072 in Cycle 1 [Time Frame: 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 of Part B]

AUC of 177Lu-IPN01072 in Blood in Cycle 1 [Time Frame: Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1]

Disease Control Rate (DCR) [Time Frame: From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.]

Maximal Uptake (%) of 177Lu-IPN01072 in Blood in Cycle 1 [Time Frame: Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1]

Terminal Half-Life (T1/2) of Radioactivity Concentrations of the Radiopharmaceutical in Blood in Cycle 1 [Time Frame: Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1]

Cumulative Amount of Lu-177 Radioactivity Excreted Into the Urine (0 to 48 Hours) [Ae (0-48h)] in Cycle 1 [Time Frame: 0 to 6 hours, 6 to 24 hours, 24 to 48 hours post-infusion in Cycle 1 of Part A; 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 of Part B.]

Time to Reach Maximum Plasma Concentration (Tmax) of IPN01072 in Cycle 1 [Time Frame: Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1]

Highest Absorbed Dose of 177LU-IPN01072 to Each Discernible Organ in Cycle 1 [Time Frame: 4, 24, 48, 72 to 96 and 144 to 168 hours post infusion in Cycle 1]

Apparent Volume of Distribution During Terminal Phase (Vz) of IPN01072 in Cycle 1 [Time Frame: Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1]

Maximum Observed Plasma Concentration (Cmax) of IPN01072 in Cycle 1 [Time Frame: Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1]

Apparent Total Plasma Clearance of IPN01072 (Total CL) in Cycle 1 [Time Frame: Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1]

Best Overall Response [Time Frame: From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.]

AUC From Time Zero to Infinity (AUCinf) of IPN01072 in Cycle 1 [Time Frame: Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1]

Area Under the Concentration Time Curve (AUC) of 177Lu-IPN01072 in Discernible Organs in Cycle 1 [Time Frame: 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1]

Cumulative Absorbed Organ Doses of 177Lu-IPN01072 in Cycles 1 and 3 [Time Frame: 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycles 1 and 3]

Specific Absorbed Dose Per Organ and Lesions of 177Lu-IPN01072 in Cycle 1 [Time Frame: 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1]

Change From Baseline in Quality of Life (QoL) Questionnaire (QLQ)-C30 at EOCT Visit [Time Frame: Baseline (Day 1) and EOCT visit (30 months)]

Maximum Uptake (%) of 177Lu-IPN01072 at Target Lesions and Discernible Organs in Cycle 1 [Time Frame: 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1]

Progression Free Survival (PFS) [Time Frame: From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.]

T1/2 of IPN01072 in Cycle 1 [Time Frame: Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1]

Overall Response Rate (ORR) [Time Frame: From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.]

Secondary ID(s)

D-FR-01072-001

2015-002867-41

OPS-C-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/07/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02592707