Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Antiemetics

Dermatologic Agents

Gastrointestinal Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Pharmaceutical Solutions

Amino Acids

Ondansetron

Dexamethasone

Somatostatin

Dexamethasone acetate

1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Serotonin

Serotonin 5-HT3 Receptor Antagonists

Neurotransmitter Agents

Chelating Agents

Arginine

Lysine

177Lu-IPN01072 administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles)

Satoreotide tetraxetan administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles)

Satoreotide tetraxetan

Given as an auxiliary product the day of the IMP infusion for safety reasons to protect the renal function.

Centres can use their established amino acid infusion or Ipsen amino acid solution (auxiliary medical product OPS301)

Amino acid solution

To counteract the known side effects of the amino acid infusion, such as nausea, dexamethasone (antiemetic) and as-required ondansetron will be administered 15 to 30 minutes before the start of the amino acid infusion (unless there are contraindications for these drugs).

Antiemetic

Ipsen Medical Director

The purpose of this clinical phase I/II study was to investigate the safety and tolerability of satoreotide tetraxetan (177Lu-IPN01072, formerly known as 177Lu-OPS201) used for the treatment of patients with neuroendocrine tumors (NETs). The secondary objectives of this study were the assessment of biodistribution, dosimetry and preliminary efficacy of satoreotide tetraxetan.

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

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)

AE is defined as any untoward medical occurrence in a subject or clinical trial subject administered a medicinal product, which did not necessarily have a causal relationship with this treatment. A serious AE (SAE) was classified as any untoward medical occurrence that at any dose results in death; AE was life threatening; required inpatient hospitalization or prolonged existing hospitalization; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect; was an important medical event that may not result in death. TEAEs are defined as AEs that developed or worsened after start of treatment.

DLTs were defined as study medication-related AEs with a severity of Grade 3 or higher are considered DLT, with the exception of hair loss, lymphopenia, nonfebrile neutropenia lasting \<4 weeks and thrombocytopenia lasting \<4 weeks.

177Lu-IPN01072 uptake in organs and lesions was evaluated centrally, using nuclear medicine images, as part of the dosimetry workflow. Uptake activity for organs of interest (i.e., body, bone marrow, kidney \[left + right\], healthy liver, and spleen) was determined. The maximal uptake in lesions was calculated for each lesion as: maximal activity divided injected activity\*100.

177Lu-IPN01072 uptake in blood was evaluated on site/locally using a gamma counter calibrated for 177Lu-IPN01072 according to the dosimetry operational manual.

The AUC of 177Lu-IPN01072 radioactivity in discernible organs were computed for each administration of 177Lu-IPN01072.

The AUC of 177Lu-IPN01072 radioactivity in blood were computed for each administration of 177Lu-IPN01072.

The terminal half-life was defined as the largest half-life of the decay curve of blood activity.

The absorbed dose to the discernible organs (i.e., organs showing uptake) was evaluated centrally, using nuclear medicine images, as part of the dosimetry workflow. The organs considered for 177LU-IPN01072 image-based dosimetry assessment included: liver, bone marrow, kidney (left + right), and spleen. Highest absorbed dose of 177Lu-IPN01072 was calculated as described in the Dosimetry calculation procedure manual. Maximum value observed for each discernible organs across participants has been reported.

The specific absorbed dose was evaluated centrally, using nuclear medicine images, as part of the dosimetry workflow. Data are presented for all lesions, regardless of their anatomical localization. The organs considered for 177Lu-IPN01072 image-based dosimetry assessment included: liver, bone marrow, kidney (left + right), and spleen. The specific absorbed dose to the lesions was the absorbed dose by the lesion (unit: Gray) divided by the injected radioactivity (unit: GBq) for each lesion selected for dosimetry evaluation. The specific absorbed dose for a given organ was the absorbed dose by this organ (unit: Gray) divided by the injected radioactivity (unit: GBq).

The cumulative absorbed dose to the discernible organs (i.e., organs showing uptake) was evaluated centrally, using nuclear medicine images, as part of the dosimetry workflow.

Urine was collected during the first 48 hours post infusion to determine the renal excretion of 177Lu-IPN01072 at Cycle 1 only.

The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only.

Urine was collected during the first 48 hours post infusion to determine the renal excretion of 177Lu-IPN01072 at Cycle 1 for Part B only.

The ORR was defined as the percentage of participants who achieved a complete response (CR) or a partial response (PR) as best overall response (BOR) according centralized to response evaluation criteria in solid tumours (RECIST) version 1.1 from investigator assessment. Participants with no tumour assessment after the start of study treatment were not evaluated. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

The DCR was defined as the percentage of participants who achieved a CR, a PR or a stable disease (SD) as BOR according to Investigator assessment RECIST version 1.1 criteria. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.

The BOR according to RECIST v1.1 was defined as the best response recorded from the initiation of treatment until the EOCT/end of additional cycles (EOAC)/early withdrawal (EW) Visit (during the core study part), prior to the Investigator assessment of PD. Progression was defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm.

The PFS was defined as the time from start of study treatment until occurrence of tumour progression or death, according to Investigator assessment RECIST version 1.1. Estimation of the median was based on the Kaplan-Meier method.

The European Organisation for Research and Treatment of Cancer (EORTC) score questionnaire (QLQ-C30) was used for QoL evaluation. Each scale in the questionnaire were scored (0 to 100) according to the EORTC recommendations in the EORTC QLQ-C30 scoring manual. The scale included a global health status, where high score for the global health status represents a high QoL. The functional scales consisted of physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, where a higher value reflects a better level of function. Nine symptoms scales included nausea and vomiting, pain, fatigue, dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties, where a higher value reflects worse symptoms. Baseline was defined as the last non-missing measurement collected prior to the first dose of study drug (Day 1).

The GI.NET21 module was intended for use among participants with gastrointestinal related (GI.- related) neuroendocrine tumours, who vary in disease stage and treatments. The module comprises 21 questions, consisting of 5 scales (endocrine symptoms, G.I. symptoms, treatment related symptom, social function, disease related worries) and 4 single items that assessed muscle /bone pain symptom, sexual function, information/communication function, and body image. Each question was quoted from 1 (not at all) to 4 (very much). Each scale in the questionnaire was scored from 0 to 100. A higher value was equivalent to worse or more problems. Baseline was defined as the last non-missing measurement collected prior to the first dose of study drug (Day 1).

Ipsen

The SAS included all participants who received study medication. Participants who received the therapeutic dose of 177Lu-IPN01072 during the core trial period in Part A and B.

Participants received 4.5 GBq 177Lu-IPN01072 (target dose of 300 mcg ±50 mcg) IV infusion on Day 1 of 3 treatment cycles. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AE which had not adequately recovered).

Part A: 177Lu-IPN01072 4.5 GBq

Participants received 6 GBq 177Lu-IPN01072 (target dose of 300 mcg) IV infusion on Day 1 of 3 treatment cycles. The radioactivity dose was reduced to 4.5 GBq in Cohort 1 adapted as recommended by DRB. As a result, Cohort 1 adapted was similar to Cohort 1 except the radioactivity dose was 4.5 GBq. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AEs which had not adequately recovered).

Part B Cohort 1: 177Lu-IPN01072 6 GBq

Participants received 4.5 GBq 177Lu-IPN01072 (target dose of 300 mcg in Cycle 1; 700 mcg in Cycle 2; 300 mcg in Cycle 3) IV infusion on Day 1 of 3 treatment cycles. Target dose was 300 mcg for additional cycles, if any. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AEs which had not adequately recovered).

Part B Cohort 3: 177Lu-IPN01072 4.5 GBq

Participants received of 4.5 GBq 177Lu-IPN01072 (target dose of 300 mcg in Cycle 1; 1300 mcg in Cycle 2; 300 mcg in Cycle 3) IV infusion on Day 1 of 3 treatment cycles. Target dose was 300 mcg for additional cycles, if any. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AEs which had not adequately recovered).

Part B Cohort 6: 177Lu-IPN01072 4.5 GBq

Participants who received 177Lu-IPN01072 dose from 4.5 to 6 GBq (target dose of 300 to 1300 mcg) as IV infusion on Day 1 of 3 treatment cycles/additional 2 cycles (when applicable). Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AE which had not adequately recovered).

All Participants

Total

Age, Continuous

>=65

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

The safety analysis set (SAS) included all participants who received 177Lu-IPN01072.

Due to strategic reasons, the Ipsen management team decided to early terminate the D-FR-01072-001 / OPS-C-001 study. This decision was not due to any safety or tolerability concern, or any event associated with the use of the study drug.

Medical Director

TEAEs

Serious TEAEs

The SAS included all participants who received 177Lu-IPN01072.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

Number of Participants With Dose Limiting Toxicities (DLT)

Bone marrow (image-based)

Liver

Kidney (left + right)

Spleen

All lesions

The Per Protocol Dosimetry Analysis Set (PP-DAS) included all participants in the Intent-To-Treat Dosimetry Analysis Set (ITT-DAS) for whom no major protocol violations occurred affecting dosimetry variables. Only data from the participants analyzed were reported.

Maximum Uptake (%) of 177Lu-IPN01072 at Target Lesions and Discernible Organs in Cycle 1

The radiopharmaceutical pharmacokinetic (PK) set included all participants in the ITT set who received at least 1 dose of study medication and had at least 1 measured radioactive concentration in blood. Only data from the participants analyzed were reported.

Maximal Uptake (%) of 177Lu-IPN01072 in Blood in Cycle 1

Bone marrow (Image-based)

The PP-DAS included all participants in the ITT-DAS for whom no major protocol violations occurred affecting dosimetry variables. Only data from the participants analyzed were reported.

Area Under the Concentration Time Curve (AUC) of 177Lu-IPN01072 in Discernible Organs in Cycle 1

The radiopharmaceutical PK set included all participants in the ITT set who received at least 1 dose of study medication and had at least 1 measured radioactive concentration in blood. Only data from the participants analyzed were reported.

AUC of 177Lu-IPN01072 in Blood in Cycle 1

Terminal Half-Life (T1/2) of Radioactivity Concentrations of the Radiopharmaceutical in Blood in Cycle 1

Bone marrow (image-based assay)

Highest Absorbed Dose of 177LU-IPN01072 to Each Discernible Organ in Cycle 1

Lesions

Participants received 3 cycles of 4.5 GBq 177Lu-IPN01072 (target dose of 300 mcg) on Day 1 of each cycle. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AEs which had not adequately recovered).

Participants received 3 cycles of 6 GBq 177Lu-IPN01072 (target dose of 300 mcg) on Day 1 of each cycle. In Cohort 1, there was an adapted radioactivity level and not adapted. In Cohort 1 adapted radioactivity dose was reduced to 4.5 GBq. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AEs which had not adequately recovered).

Participants received 3 cycles of 4.5 GBq 177Lu-IPN01072 (target dose of 300 mcg in Cycle 1; 700 mcg in Cycle 2; 300 mcg in Cycle 3; 300 mcg for additional cycles of 4 and 5) on Day 1 of each cycle. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AEs which had not adequately recovered).

Participants received 3 cycles of 4.5 GBq 177Lu-IPN01072 (target dose of 300 mcg in Cycle 1; 1300 mcg in Cycle 2; 300 mcg in Cycle 3; 300 mcg for additional cycles of 4 and 5) on Day 1 of each cycle. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AEs which had not adequately recovered).

Specific Absorbed Dose Per Organ and Lesions of 177Lu-IPN01072 in Cycle 1

Cycle 1: Bone marrow (image-based)

Cycle 1: Kidney (left + right)

Cycle 1: Liver

Cycle 1: Spleen

Cycle 3: Bone marrow (image-based)

Cycle 3: Kidney (left + right)

Cycle 3: Liver

Cycle 3: Spleen

Cumulative Absorbed Organ Doses of 177Lu-IPN01072 in Cycles 1 and 3

The Radiopharmaceutical PK Set (Part A and Part B) included all participants in the ITT set who received at least 1 dose of study medication and had at least 1 measured radioactive concentration in blood.

Cumulative Amount of Lu-177 Radioactivity Excreted Into the Urine (0 to 48 Hours) [Ae (0-48h)] in Cycle 1

IPN01072 PK monitoring was performed on cycle 1 only. Participants received 177Lu-IPN01072 dose from 4.5 to 6 GBq (target IPN01072 dose 300 mcg) as IV infusion on Day 1 cycle. The radioactivity dose was reduced to 4.5 GBq in Cohort 1 adapted as recommended by DRB. As a result, Cohort 1 adapted was similar to Cohort 1 except the radioactivity dose was 4.5 GBq. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AEs which had not adequately recovered).

Part B: All Participants

The IPN01072 PK set in plasma (Part B only) included all participants in the ITT set who received at least 1 dose of study medication and have no major protocol deviations affecting the plasma PK variables and who had a sufficient number of plasma levels to estimate the main PK parameters. Only data from the participants analyzed were reported. Results were combined for IPN01072 PK analysis performed at cycle 1, as pre-specified according to study protocol and the data analysis plan.

Time to Reach Maximum Plasma Concentration (Tmax) of IPN01072 in Cycle 1

Maximum Observed Plasma Concentration (Cmax) of IPN01072 in Cycle 1

AUC From Time Zero to Infinity (AUCinf) of IPN01072 in Cycle 1

T1/2 of IPN01072 in Cycle 1

Apparent Total Plasma Clearance of IPN01072 (Total CL) in Cycle 1

Apparent Volume of Distribution During Terminal Phase (Vz) of IPN01072 in Cycle 1

The IPN01072 PK set in urine (Part B only) included all participants in the ITT set who received at least 1 dose of study medication and have no major protocol deviations affecting the urine PK variables and who had all urine IPN01072 levels to estimate the main urine PK parameters. Results were combined for IPN01072 PK analysis performed at cycle 1, as pre-specified according to study protocol and the data analysis plan.

Ae (0-48h) of IPN01072 in Cycle 1

The IPN01072 PK set in urine (Part B only) included all participants in the ITT set who received at least 1 dose of study medication and had no major protocol deviations affecting the urine PK variables and who had all urine IPN01072 levels available to estimate the main urine PK parameters. Results were combined for IPN01072 PK analysis performed at cycle 1, as pre-specified according to study protocol and the data analysis plan.

Fraction of IPN01072 Excreted Into the Urine (Fe) in Cycle 1

The ITT included all participants in the eligible participants set who received study medication.

Overall Response Rate (ORR)

Disease Control Rate (DCR)

Best Overall Response

Progression Free Survival (PFS)

Global Health Status

Physical functioning

Role functioning

Emotional functioning

Cognitive functioning

Social functioning

The ITT included all participants in the eligible participants set who received study medication. Only data from the participants analyzed were reported.

Change From Baseline in Quality of Life (QoL) Questionnaire (QLQ)-C30 at EOCT Visit

Endocrine symptoms

G. I. symptoms

Treatment related symptom

Social function

Disease related worries

Change From Baseline in QLQ Gastro-intestinal. Neuroendocrine Tumour (GI.NET)21 at EOCT Visit

Participants received 4.5 gigabecquerel (GBq) 177Lu-IPN01072 \[target dose of 300 microgram (mcg) ±50 mcg\] intravenous (IV) infusion on Day 1 of 3 treatment cycles. Each cycle was 8 weeks apart \[+2 weeks or up to +4 weeks in case of adverse events (AE) which had not adequately recovered\].

Participants received 6 GBq 177Lu-IPN01072 (target dose of 300 mcg) IV infusion on Day 1 of 3 treatment cycles. The radioactivity dose was reduced to 4.5 GBq in Cohort 1 adapted as recommended by data review board (DRB). As a result, Cohort 1 adapted was similar to Cohort 1 except the radioactivity dose was 4.5 GBq. Each cycle was 8 weeks apart (+2 weeks or up to +4 weeks in case of AEs which had not adequately recovered).

Spots Global Cancer Trial Database for Study to Evaluate the Safety and Preliminary Efficacy of 177Lu-OPS201 in NETs

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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