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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002867-41 | EudraCT Number | ||
| OPS-C-001 | Other Identifier | Initial sponsor study ID |
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Terminated (Due to small number of ongoing patients. Patients ongoing at time of termination could choose to join study D-FR-01072-004 for long term follow-up.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 177Lu-IPN01072 | Experimental | 177Lu-IPN01072 administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Satoreotide tetraxetan | Drug | Satoreotide tetraxetan administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | 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. | 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 |
| Number of Participants With Dose Limiting Toxicities (DLT) | 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. | From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Uptake (%) of 177Lu-IPN01072 at Target Lesions and Discernible Organs in Cycle 1 | 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. |
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Inclusion Criteria:
Written informed consent.
Patients of either gender, aged ≥ 18 years.
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.).
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.
Karnofsky performance score ≥ 60.
Life expectancy of at least 6 months.
Histologically confirmed diagnosis of -
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.
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.
Measurable disease based on RECIST v1.1.
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.
Calculated GFR ≥ 55 mL/min.
Blood test results as follows:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MD Anderson Cancer Center, Department of Nuclear Medicine | Houston | Texas | 77030 | United States | ||
| Peter MacCallum Cancer Centre, Molecular Imaging and Targeted Therapeutics Laboratory |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38528164 | Derived | Schurrle SB, Eberlein U, Ansquer C, Beauregard JM, Durand-Gasselin L, Gronbaek H, Haug A, Hicks RJ, Lenzo NP, Navalkissoor S, Nicolas GP, Pais B, Volteau M, Wild D, McEwan A, Lassmann M. Dosimetry and pharmacokinetics of [177Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2024 Jul;51(8):2428-2441. doi: 10.1007/s00259-024-06682-1. Epub 2024 Mar 26. | |
| 37721581 |
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The study was performed in 2 parts, Part A and Part B. Study consists of a screening period (up to 4 weeks), Treatment period (3 core treatment cycles in each Part A and Part B; 2 additional cycles in Part B only) and followed by long-term follow-up (LTFU) period (2 years). Each cycle was 8 weeks (+ up to 4 weeks if toxicity) apart. A total 40 participants were treated in this study. Due to initial findings, Cohorts 2, 4, 5, 7 and 8 in Part B were not performed in this study.
This Phase 1/2, open-label study was conducted in participants with somatostatin receptor positive neuroendocrine tumour (NETs) at 8 investigational sites in Australia, Austria, Canada, Denmark, France, Switzerland and United Kingdom between 06 March 2017 and 22 February 2022. The sponsor terminated the study early for strategic reasons and this decision was not due to any safety or tolerability concern of the study drug.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: 177Lu-IPN01072 4.5 GBq | 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]. |
| FG001 | Part B Cohort 1: 177Lu-IPN01072 6 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 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). |
| FG002 | Part B Cohort 3: 177Lu-IPN01072 4.5 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). |
| FG003 | Part B Cohort 6: 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
The safety analysis set (SAS) included all participants who received 177Lu-IPN01072.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: 177Lu-IPN01072 4.5 GBq | 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). |
| BG001 | Part B Cohort 1: 177Lu-IPN01072 6 GBq |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | 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. | The SAS included all participants who received 177Lu-IPN01072. | Posted | Count of Participants | Participants | No | 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 |
|
Treatment-emergent adverse events were collected from the start of the first study medication (Cycle 1 Day 1) up to 6 months after the last dose of study medication, a maximum of 33 months.
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A: 177Lu-IPN01072 4.5 GBq | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Myeloid Leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Ipsen Pharma | see email | clinical.trials@ipsen.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 10, 2020 | Feb 15, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 9, 2021 | Feb 15, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| ID | Term |
|---|---|
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000608229 | 177Lu-DOTA-JR11 |
| C545824 | amino-acid, glucose, and electrolyte solution |
| C104090 | arginyllysine |
| D000932 | Antiemetics |
| D003907 | Dexamethasone |
| D017294 | Ondansetron |
| ID | Term |
|---|---|
| D001337 | Autonomic Agents |
| D018373 | Peripheral Nervous System Agents |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
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| Amino acid solution | Other | 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) |
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| Antiemetic | Other | 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). |
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| 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
| Maximal Uptake (%) of 177Lu-IPN01072 in Blood in Cycle 1 | 177Lu-IPN01072 uptake in blood was evaluated on site/locally using a gamma counter calibrated for 177Lu-IPN01072 according to the dosimetry operational manual. | Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
| Area Under the Concentration Time Curve (AUC) of 177Lu-IPN01072 in Discernible Organs in Cycle 1 | The AUC of 177Lu-IPN01072 radioactivity in discernible organs were computed for each administration of 177Lu-IPN01072. | 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
| AUC of 177Lu-IPN01072 in Blood in Cycle 1 | The AUC of 177Lu-IPN01072 radioactivity in blood were computed for each administration of 177Lu-IPN01072. | 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 | The terminal half-life was defined as the largest half-life of the decay curve of blood activity. | Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
| Highest Absorbed Dose of 177LU-IPN01072 to Each Discernible Organ in Cycle 1 | 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. | 4, 24, 48, 72 to 96 and 144 to 168 hours post infusion in Cycle 1 |
| Specific Absorbed Dose Per Organ and Lesions of 177Lu-IPN01072 in Cycle 1 | 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). | 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 | 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. | 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycles 1 and 3 |
| Cumulative Amount of Lu-177 Radioactivity Excreted Into the Urine (0 to 48 Hours) [Ae (0-48h)] in Cycle 1 | Urine was collected during the first 48 hours post infusion to determine the renal excretion of 177Lu-IPN01072 at Cycle 1 only. | 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 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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 |
| AUC From Time Zero to Infinity (AUCinf) of IPN01072 in Cycle 1 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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 |
| T1/2 of IPN01072 in Cycle 1 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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 Volume of Distribution During Terminal Phase (Vz) of IPN01072 in Cycle 1 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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 |
| Ae (0-48h) of IPN01072 in Cycle 1 | 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. | 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 of Part B |
| Fraction of IPN01072 Excreted Into the Urine (Fe) in Cycle 1 | 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. | 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 in Part B |
| Overall Response Rate (ORR) | 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. | 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. |
| Disease Control Rate (DCR) | 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. | 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. |
| Best Overall Response | 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. | 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. |
| Progression Free Survival (PFS) | 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. | 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. |
| Change From Baseline in Quality of Life (QoL) Questionnaire (QLQ)-C30 at EOCT Visit | 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). | Baseline (Day 1) and EOCT visit (30 months) |
| Change From Baseline in QLQ Gastro-intestinal. Neuroendocrine Tumour (GI.NET)21 at EOCT Visit | 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). | Baseline (Day 1) and EOCT visit (30 months) |
| East Melbourne |
| 3002 |
| Australia |
| Ramsay Hollywood Private Hospital, Department of Nuclear Medicine | Perth | 6009 | Australia |
| University Hospital Vienna, Department of Nuclear Medicine | Vienna | 1090 | Austria |
| CHU de Quebec - Universite Laval Research Center, Department of Radiology and Nuclear Medicine | Québec | G1R2J6 | Canada |
| University Hospital Aarhus, Department of Hepatology and Gastroenterology | Aarhus | 8000 | Denmark |
| CHU de Nantes, Hotel Dieu, Service de Medecine Nucleaire | Nantes | 44093 | France |
| University Hospital Basel, Department of Nuclear Medicine | Basel | 4031 | Switzerland |
| Royal Free Hospital, Department of Nuclear Medicine | London | NW3 2QG | United Kingdom |
| Derived |
| Wild D, Gronbaek H, Navalkissoor S, Haug A, Nicolas GP, Pais B, Ansquer C, Beauregard JM, McEwan A, Lassmann M, Pennestri D, Volteau M, Lenzo NP, Hicks RJ. A phase I/II study of the safety and efficacy of [177Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2023 Dec;51(1):183-195. doi: 10.1007/s00259-023-06383-1. Epub 2023 Sep 18. |
| Death |
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| Progressive Disease |
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| Other |
|
| Never entered LTFU period |
|
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). |
| BG002 | Part B Cohort 3: 177Lu-IPN01072 4.5 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). |
| BG003 | Part B Cohort 6: 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). |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants | No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
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). |
| OG001 | Part B Cohort 1: 177Lu-IPN01072 6 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). |
| OG002 | Part B Cohort 3: 177Lu-IPN01072 4.5 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). |
| OG003 | Part B Cohort 6: 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). |
| OG004 | All Participants | 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). |
|
|
| Primary | Number of Participants With Dose Limiting Toxicities (DLT) | 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. | The SAS included all participants who received 177Lu-IPN01072. | Posted | Count of Participants | Participants | No | From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks. |
|
|
|
| Secondary | Maximum Uptake (%) of 177Lu-IPN01072 at Target Lesions and Discernible Organs in Cycle 1 | 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. | 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. | Posted | Median | Full Range | percentage of injected drug activity | 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
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| Secondary | Maximal Uptake (%) of 177Lu-IPN01072 in Blood in Cycle 1 | 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 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. | Posted | Median | Full Range | percentage/liter (L) | Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
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| Secondary | Area Under the Concentration Time Curve (AUC) of 177Lu-IPN01072 in Discernible Organs in Cycle 1 | The AUC of 177Lu-IPN01072 radioactivity in discernible organs were computed for each administration of 177Lu-IPN01072. | 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. | Posted | Median | Full Range | MBq*hour | 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
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|
| Secondary | AUC of 177Lu-IPN01072 in Blood in Cycle 1 | The AUC of 177Lu-IPN01072 radioactivity in blood were computed for each administration of 177Lu-IPN01072. | 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. | Posted | Median | Full Range | MBq*hour/L | Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
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| Secondary | Terminal Half-Life (T1/2) of Radioactivity Concentrations of the Radiopharmaceutical in Blood in Cycle 1 | The terminal half-life was defined as the largest half-life of the decay curve of blood activity. | 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. | Posted | Median | Full Range | hours | Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
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| Secondary | Highest Absorbed Dose of 177LU-IPN01072 to Each Discernible Organ in Cycle 1 | 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 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. | Posted | Number | Gray | 4, 24, 48, 72 to 96 and 144 to 168 hours post infusion in Cycle 1 |
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| Secondary | Specific Absorbed Dose Per Organ and Lesions of 177Lu-IPN01072 in Cycle 1 | 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 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. | Posted | Median | Full Range | Gray/GBq | 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1 |
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| Secondary | Cumulative Absorbed Organ Doses of 177Lu-IPN01072 in Cycles 1 and 3 | 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. | 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. | Posted | Median | Full Range | Gray | 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycles 1 and 3 |
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| Secondary | Cumulative Amount of Lu-177 Radioactivity Excreted Into the Urine (0 to 48 Hours) [Ae (0-48h)] in Cycle 1 | Urine was collected during the first 48 hours post infusion to determine the renal excretion of 177Lu-IPN01072 at Cycle 1 only. | 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. | Posted | Median | Full Range | Mbq | 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. |
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| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of IPN01072 in Cycle 1 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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. | Posted | Median | Full Range | hours | 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 |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of IPN01072 in Cycle 1 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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. | Posted | Mean | Standard Deviation | nanogram (ng)/milliliter (mL) | 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 |
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| Secondary | AUC From Time Zero to Infinity (AUCinf) of IPN01072 in Cycle 1 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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. | Posted | Mean | Standard Deviation | ng*hour (h)/mL | 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 |
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| Secondary | T1/2 of IPN01072 in Cycle 1 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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. | Posted | Mean | Standard Deviation | hours | 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 |
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| Secondary | Apparent Total Plasma Clearance of IPN01072 (Total CL) in Cycle 1 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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. | Posted | Mean | Standard Deviation | L/h | 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 |
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| Secondary | Apparent Volume of Distribution During Terminal Phase (Vz) of IPN01072 in Cycle 1 | The PK sampling was performed from Day 1 to Day 3 post infusion done at Cycle 1 for Part B only. | 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. | Posted | Mean | Standard Deviation | Liter | 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 |
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| Secondary | Ae (0-48h) of IPN01072 in Cycle 1 | 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 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. | Posted | Mean | Standard Deviation | mcg | 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 of Part B |
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| Secondary | Fraction of IPN01072 Excreted Into the Urine (Fe) in Cycle 1 | 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 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. | Posted | Mean | Standard Deviation | percentage of drug excreted into urine | 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 in Part B |
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| Secondary | Overall Response Rate (ORR) | 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 ITT included all participants in the eligible participants set who received study medication. | Posted | Number | 95% Confidence Interval | percentage of participants | 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. |
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| Secondary | Disease Control Rate (DCR) | 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 ITT included all participants in the eligible participants set who received study medication. | Posted | Number | 95% Confidence Interval | percentage of participants | 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. |
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| Secondary | Best Overall Response | 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 ITT included all participants in the eligible participants set who received study medication. | Posted | Count of Participants | Participants | No | 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. |
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| Secondary | Progression Free Survival (PFS) | 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 ITT included all participants in the eligible participants set who received study medication. | Posted | Median | 95% Confidence Interval | months | 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. |
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| Secondary | Change From Baseline in Quality of Life (QoL) Questionnaire (QLQ)-C30 at EOCT Visit | 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 ITT included all participants in the eligible participants set who received study medication. Only data from the participants analyzed were reported. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1) and EOCT visit (30 months) |
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| Secondary | Change From Baseline in QLQ Gastro-intestinal. Neuroendocrine Tumour (GI.NET)21 at EOCT Visit | 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). | The ITT included all participants in the eligible participants set who received study medication. Only data from the participants analyzed were reported. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1) and EOCT visit (30 months) |
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| 2 |
| 15 |
| 2 |
| 15 |
| 15 |
| 15 |
| EG001 | Part B Cohort 1: 177Lu-IPN01072 6 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). | 0 | 6 | 1 | 6 | 6 | 6 |
| EG002 | Part B Cohort 3: 177Lu-IPN01072 4.5 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). | 0 | 9 | 2 | 9 | 9 | 9 |
| EG003 | Part B Cohort 6: 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). | 1 | 10 | 3 | 10 | 10 | 10 |
| EG004 | All Participants | 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). | 3 | 40 | 8 | 40 | 39 | 40 |
| Malignant Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
|
| Precursor B-Lymphoblastic Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Systemic Inflammatory Response Syndrome | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Ankle Fracture | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
|
| Tumour Marker Increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Gastrointestinal Sounds Abnormal | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Abdominal Discomfort | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Abdominal Distension | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Dry Mouth | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Abdominal Pain Lower | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Abnormal Faeces | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Anorectal Discomfort | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Breath Odour | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Dental Caries | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Epigastric Discomfort | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Frequent Bowel Movements | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Gastrointestinal Motility Disorder | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Gingival Bleeding | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Lip Dry | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Odynophagia | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Paraesthesia Oral | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Steatorrhoea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Infusion site reaction | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Discomfort | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Injection site bruising | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Sense of oppression | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Xerosis | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Parosmia | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Taste disorder | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypogeusia | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Sensory disturbance | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Myelosuppression | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Anal fungal infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Groin abscess | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Perineal infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Protein urine present | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Albumin urine present | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Bilirubin urine present | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Blood pressure decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Cardiac murmur | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Cortisol decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Creatinine renal clearance decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Electrocardiogram ambulatory abnormal | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Liver function test increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Lung cyst | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
|
| Burn oesophageal | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
|
| Occupational exposure to radiation | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Supraventricular extrasystoles | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Arrhythmia | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Increased appetite | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Affective disorder | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Deafness neurosensory | Ear and labyrinth disorders | MedDRA (23.1) | Systematic Assessment |
|
| Deafness unilateral | Ear and labyrinth disorders | MedDRA (23.1) | Systematic Assessment |
|
| External ear pain | Ear and labyrinth disorders | MedDRA (23.1) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (23.1) | Systematic Assessment |
|
| Vestibular disorder | Ear and labyrinth disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hepatic pain | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment |
|
| Product leakage | Product Issues | MedDRA (23.1) | Systematic Assessment |
|
| Microalbuminuria | Renal and urinary disorders | MedDRA (23.1) | Systematic Assessment |
|
| Ovarian Cyst | Reproductive system and breast disorders | MedDRA (23.1) | Systematic Assessment |
|
Not provided
| D009380 | Neoplasms, Nerve Tissue |
| D020164 | Chemical Actions and Uses |
| D002491 | Central Nervous System Agents |
| D045506 | Therapeutic Uses |
| D005765 | Gastrointestinal Agents |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006575 | Heterocyclic Compounds, 3-Ring |
|
| Liver |
|
|
| Kidney (left + right) |
|
|
| Spleen |
|
|
| All lesions |
|
|
|
| Kidney (left + right) |
|
|
| Liver |
|
|
| Spleen |
|
|
|
| Kidney (left + right) |
|
|
| Liver |
|
|
| Spleen |
|
|
|
| Bone marrow (image-based) |
|
|
| Kidney (left + right) |
|
|
| Liver |
|
|
| Spleen |
|
|
|
| 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 |
|
|
| SD |
|
| PD |
|
| Not Evaluable (NE) |
|
|
| Physical functioning |
|
|
| Role functioning |
|
|
| Emotional functioning |
|
|
| Cognitive functioning |
|
|
| Social functioning |
|
|
| G. I. symptoms |
|
| Treatment related symptom |
|
| Social function |
|
| Disease related worries |
|