Advanced Cancer, Bone Cancer, Colorectal Cancer, Gastric Cancer, Metastatic Tumours, Pancreatic Ductal Adenocarcinoma, Recurrent Disease, Squamous Cell Carcinoma of the Head and Neck
Conditions
Brief summary
This study was conducted to advance new treatment for patients with metastatic or locally advanced cancers expressing Neurotensin receptor 1 (NTSR1). This study was the first time the investigational drug called 177Lu-3BP-227 was administered to patients under controlled conditions of a clinical study. The purpose of this study was to evaluate how safe the investigational drug is as well to verify how well it is tolerated by patients after several intravenous administrations. In addition, the effect of the study drug on tumoral lesions and how it distributes throughout the body and at which rate it is removed from the body was evaluated. Since 177Lu-3BP-227 is a radio-labelled drug, it also measured how the emitted radiation is distributed throughout the body (dosimetry). The study consisted of a phase I dose escalation part. The study originally planned to include a phase II study however due to early termination (not due to safety concerns) the study did not progress to phase II and was stopped during phase I. For the phase I dose escalation part, it was anticipated that approximately 30 subjects will be included, in up to six escalation steps. No expansion cohorts were implemented.
Interventions
DRUG177Lu-3BP-227 (also called 177Lu-IPN01087)
The cumulative activity of the treatment investigational medicinal product (IMP) formulation will be administered in two intravenous (i.v.) infusions separated by at least 4 weeks (28 days). Up to 6 administrations can be given (2 cycles plus 4 optional additional)
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Signed informed consent form prior to all study procedures * Aged 18 years or older. * Histologically or cytologically confirmed unresectable locally advanced or metastatic disease and has received prior lines of standard-of-care chemotherapy/treatment and has no further suitable treatment options and documented decision by a multidisciplinary oncology board including a specialist of the concerned pathology. * Subjects have (a) pancreatic ductal adenocarcinoma (PDAC), or (b) colorectal adenocarcinoma (CRC), or (c) gastric adenocarcinoma (GC), or (d) gastrointestinal stromal tumours (GIST), or (e) squamous-cell carcinoma of head and neck (SCCHN), or (f) Ewing Sarcoma (ES) * Tumour showing: (a) by uptake of 177Lu-3BP-227 (screening formulation) in known primary or metastatic sites as judged by the investigator to be greater than background; or (b) uptake of 111In 3BP 227 in known primary or metastatic sites (for subjects who participated in Study D FR 01087 002) as judged by the investigator to be greater than background. * Measurable disease (based on RECIST version1.1). * Documentation of progressive disease in the 6 months prior to study start (treatment). * Eastern Cooperative Oncology Group performance status of 0 or 1 (unless if disability is related to surgery in ES and Agreed with the Sponsor). * Adequate organ function as evidenced by: (a) Leukocytes ≥3000/μL (b) Absolute neutrophil count ≥1500/µL (c) Platelets ≥75,000/µL (d) Hb \>9 g/dL or \>10 g/dL (if history of cardiac disease) (e) Total serum bilirubin ≤2 times upper normal institutional limits (ULN) (f) Aspartate aminotransferase/alanine aminotransferase (ALT) ≤2.5×ULN (or ≤5×ULN, if subject has liver metastases) (g) Estimated glomerular filtration rate (eGFR) ≥55 mL/min. * Estimated life expectancy \>3 months. * Female subjects must not be pregnant or lactating at study entry and during the course of the study and must not become pregnant for at least 6 months following the last study treatment. Women of childbearing potential must agree to use a highly effective method of contraception * For male subjects, must not father children during the study and for at least 6 months after the last study treatment and in addition must agree to use a condom for this period to protect his partner from contamination with the IMP. For males with partners who are of child bearing potential, effective contraception is a combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods), but these are not considered to be highly effective. A man is considered to be infertile if he has had bilateral orchidectomy or successful vasectomy. Effective contraception includes a female partner of childbearing potential if she is using highly efficacious contraception, but the male subject must agree to use a condom to protect his partner as described above. * Must be willing and able to comply with study restrictions and to remain at the clinic for the required time during the study period and willing to return to the clinic for the follow-up evaluation, as specified in the protocol.
Exclusion criteria
: * Prior treatment received (a) Any antitumor treatment since last documented disease progression (b) Any chemotherapy within 3 weeks or nitrosourea within 6 weeks prior to first treatment investigational medicinal product (IMP) administration (c) Any curative radiotherapy within 4 weeks, or palliative radiotherapy within 7 days prior to first treatment IMP administration (d) Any monoclonal antibodies within 4 weeks or tyrosine kinases inhibitors within 2 weeks prior to the first treatment IMP administration, (e) Any other IMP within 2 weeks prior to first treatment IMP administration, if the previous compound is a mechanism-based molecularly targeted agent whose half-life (t1/2) is not well-characterized. * Brain metastases. * Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject at high risk of renal toxicity during the study. * Only non-measurable metastatic bone lesions * Existing or planned colostomy during study participation. * Any history of inflammatory bowel disease. * Any uncontrolled significant medical, psychiatric or surgical condition or laboratory finding, that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results. * Clinically significant abnormalities on electrocardiogram (ECG) at screening including corrected QT interval (Fridericia's formula) \>450 msec for males or 470 msec for females at screening. * Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys. * Any unresolved NCI-CTCAE Grade 2 or higher toxicity (except alopecia) from previous antitumor treatment and/or medical/surgical procedures/interventions. * Known allergy to IMP or its excipients administered in this study, including imaging contrast media. * Positive pregnancy test (female subjects). * Likely to be uncompliant or uncooperative during the study, in the judgment of the investigator. * Unable to understand the nature, scope, and possible consequences of the study, in the judgment of the investigator. * Sponsor employees or investigator site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT) | From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks. | DLTs were defined for a list of predefined study medication-related adverse events (AEs) as specified in the protocol, according to the National Cancer Institute - Common Terminology Criteria for Adverse Events scale version 5.0 that occurred during the defined DLT assessment period (during Cycle 1 or 2). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Maximal Concentration (Cmax) of 177Lu-3BP-227 | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle. | The pharmacokinetic (PK) sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle. |
| Phase 1: Time Post Injection to Achieve Cmax of 177Lu-3BP-227 | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle. | The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle. |
| Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of 177Lu-3BP-227 | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle. | The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle. |
| Phase 1: Half-life (t1/2) of 177Lu-3BP-227 | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle. | The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle. |
| Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. | The absorbed dose to the target lesions and discernible organs (i.e., organs showing uptake) was evaluated by image-based analysis. The organs considered for 177Lu-3BP-227 image-based dosimetry assessment included: healthy liver, total liver, bone marrow, left kidney, right kidney, intestine (large and small), spleen, pancreas, stomach wall, right ovary, left ovary, uterus, right testis, left testis, thymus, right thyroid gland, left thyroid gland, prostate gland and total body. The organ that had the highest absorbed dose of treatment for each participant in each treatment cycle was determined. |
| Phase 1: Specific Absorbed Dose to the Target Lesions of 177Lu-3BP-227 | From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. | The specific absorbed dose to the target lesions was evaluated by image-based analysis. Results for all studied diseases (pancreatic ductal adenocarcinoma and colorectal carcinoma) at all anatomical locations (cervical, intrapelvic, liver, lung, lymph node, and pancreas) for all cycles (Cycle 1 and 2) are reported. The specific absorbed dose (Gray/GBq) was calculated as the absorbed dose to the target lesions (in Gray) divided by the activity of 177Lu-3BP-227 administered (in GBq). |
| Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227 | From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. | The specific absorbed dose per organ was evaluated by image-based analysis. The specific absorbed dose (Gray/GBq) was calculated as the absorbed dose to an organ (in Gray) divided by the activity of 177Lu-3BP-227 administered (in GBq). |
| Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. | The cumulative absorbed dose to the discernible organs (i.e., organs showing uptake) was evaluated by image-based analysis. |
| Phase 1: Cmax of 3BP-227 | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. | The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. |
| Phase 1: AUC of 3BP-227 | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. | The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. |
| Phase 1: t1/2 of 3BP-227 | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. | The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. |
| Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs | Measurements were performed at 0 to 1 hours, 2 to 4 hours, 16 to 24 hours, 40 to 48 hours, 72 to 96 hours post infusion in each treatment cycle. | 177Lu-3BP-227 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, left kidney, right kidney, healthy liver, and spleen) was determined. The uptake activity was expressed relatively to the injected 177Lu-3BP-227 activity calculated as the ratio of the uptake activity divided by the administered activity at the time of injection. |
| Phase 1: Volume of Distribution of 3BP-227 | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. | The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. |
| Phase 1: Cumulative Amount of Unchanged 3BP-227 Excreted Into the Urine | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. | The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. |
| Phase 1: Renal Clearance of 3BP-227 From Plasma | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. | The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. |
| Phase 1: Number of Participants With Objective Response Rate (ORR) | From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. | The ORR was defined as number of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) relative to the total number of evaluable participants. |
| Phase 1: Number of Participants With Disease Control Rate (DCR) | From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. | The DCR was defined as number of participants with a BOR characterized as CR, PR or stable disease according to RECIST 1.1 relative to the total number of evaluable participants. |
| Phase 1: Progression-Free Survival (PFS) | From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. | The PFS was defined as the time from date of first study medication administration until progression, according to RECIST 1.1. |
| Phase 1: Overall Survival (OS) | From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. | The OS was defined from first study medication administration until death, according to RECIST 1.1. |
| Phase 1: Metabolic Tumor Response Using Positron Emission Tomography (PET) Response Criteria In Solid Tumors (PERCIST) Version 1.0 or Practical PERCIST | From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. | Tumor response assessments were planned to perform by the site investigator (local) for the phase 1 and dose escalation part and by independent reader (central) for the phase 2. All fluorine-18 fluorodeoxyglucose-PET images were used for the metabolic tumor response assessments as described in PERCIST version 1.0 by the Investigator and/or independent readers. |
| Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal | Changes in tumor markers in serum relevant and specific to the underlying tumor disease was determined. |
| Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal | Changes in tumor markers in serum relevant and specific to the underlying tumor disease was determined. |
| Phase 1: Clearance of 3BP-227 | Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. | The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1. |
Countries
Belgium, France, Netherlands, Switzerland, United States
Participant flow
Recruitment details
This Phase 1/2 first in human study was conducted in participants with unresectable, locally advanced or metastatic solid tumors expressing neurotensin receptor 1 (NTSR1) at 9 investigational sites in Belgium, France, the Netherlands, Switzerland and USA between 03 May 2018 and 28 April 2021. The sponsor terminated the study early during Cohort 5 in phase 1 dose escalation; phase 1 dose expansion and phase 2 were not started.
Pre-assignment details
For phase 1, the core trial was up to 19 weeks (including screening) and comprised of 2 treatment cycles. If a participant had clinical benefit (Investigator judgment), they could receive up to 4 additional cycles after end of core trial (EOCT) provided certain other criteria were met. Long-term follow-up period was up to 5 years. Due to early termination, only results of the core trial are presented. 14 participants received a therapeutic dose of 177Lu-3BP-227 in phase 1 of the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq Participants received 177Lu-3BP-227 2.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period. | 2 |
| Cohort 2: 177Lu-3BP-227 4.0 GBq Participants received 177Lu-3BP-227 4.0 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period. | 3 |
| Cohort 3: 177Lu-3BP-227 5.5 GBq Participants received 177Lu-3BP-227 5.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period. | 5 |
| Cohort 4: 177Lu-3BP-227 6.5 GBq Participants received 177Lu-3BP-227 6.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period. | 3 |
| Cohort 5: 177Lu-3BP-227 7.5 GBq Participants received 177Lu-3BP-227 7.5 GBq fractionated into 2 IV administrations separated by 4 to 5 weeks during the core trial period. | 1 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 2 | 0 | 0 |
| Overall Study | Progressive disease | 0 | 1 | 1 | 3 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: 177Lu-3BP-227 2.5 GBq | Cohort 2: 177Lu-3BP-227 4.0 GBq | Cohort 3: 177Lu-3BP-227 5.5 GBq | Cohort 4: 177Lu-3BP-227 6.5 GBq | Cohort 5: 177Lu-3BP-227 7.5 GBq | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 70.0 years STANDARD_DEVIATION 4.2 | 64.3 years STANDARD_DEVIATION 16.2 | 64.0 years STANDARD_DEVIATION 7.2 | 66.3 years STANDARD_DEVIATION 9.1 | 77.0 years | 66.4 years STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized American Indian / Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black / African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian / Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants | 3 Participants | 1 Participants | 14 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not Collected | 2 Participants | 3 Participants | 5 Participants | 0 Participants | 0 Participants | 10 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 0 / 3 | 2 / 5 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 2 / 2 | 3 / 3 | 5 / 5 | 3 / 3 | 0 / 1 |
| serious Total, serious adverse events | 2 / 2 | 2 / 3 | 5 / 5 | 3 / 3 | 0 / 1 |
Outcome results
Primary
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT)
DLTs were defined for a list of predefined study medication-related adverse events (AEs) as specified in the protocol, according to the National Cancer Institute - Common Terminology Criteria for Adverse Events scale version 5.0 that occurred during the defined DLT assessment period (during Cycle 1 or 2).
Time frame: From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks.
Population: Safety population contained all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
Secondary
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of 177Lu-3BP-227
The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: AUC of 3BP-227
The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: Clearance of 3BP-227
The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: Cmax of 3BP-227
The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227
The cumulative absorbed dose to the discernible organs (i.e., organs showing uptake) was evaluated by image-based analysis.
Time frame: From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
Population: Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis. Cumulative absorbed doses on Cycles 1 and 2 are only presented for participants who have performed the 2 cycles.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Bone marrow | 0.326 Gray |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Healthy liver | 0.254 Gray |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Left kidney | 2.17 Gray |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Right kidney | 2.38 Gray |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Bone marrow | 0.604 Gray |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Right kidney | 3.39 Gray |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Healthy liver | 0.353 Gray |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Left kidney | 4.19 Gray |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Right kidney | 2.97 Gray |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Healthy liver | 0.530 Gray |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Left kidney | 3.33 Gray |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Bone marrow | 0.680 Gray |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Bone marrow | 0.820 Gray |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Healthy liver | 0.714 Gray |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Right kidney | 3.01 Gray |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Left kidney | 3.44 Gray |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Left kidney | 2.95 Gray |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Right kidney | 2.92 Gray |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Healthy liver | 0.571 Gray |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 | Cycle 2: Bone marrow | 0.694 Gray |
Secondary
Phase 1: Cumulative Amount of Unchanged 3BP-227 Excreted Into the Urine
The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: Half-life (t1/2) of 177Lu-3BP-227
The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: Maximal Concentration (Cmax) of 177Lu-3BP-227
The pharmacokinetic (PK) sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs
177Lu-3BP-227 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, left kidney, right kidney, healthy liver, and spleen) was determined. The uptake activity was expressed relatively to the injected 177Lu-3BP-227 activity calculated as the ratio of the uptake activity divided by the administered activity at the time of injection.
Time frame: Measurements were performed at 0 to 1 hours, 2 to 4 hours, 16 to 24 hours, 40 to 48 hours, 72 to 96 hours post infusion in each treatment cycle.
Population: Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis. Since the study drug administered to different groups had same composition/specific activity, no difference in drug distribution was expected between groups. Because uptake results were expressed as percentage of administered 177Lu-3BP-227 activity, no difference in uptake was expected between groups and results were reported combining all groups.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs | All cycles: Body | 99.7 percentage of injected 177Lu-3BP-227 |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs | All cycles: Bone marrow | 1.10 percentage of injected 177Lu-3BP-227 |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs | All cycles: Left kidney | 0.247 percentage of injected 177Lu-3BP-227 |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs | All cycles: Right kidney | 0.227 percentage of injected 177Lu-3BP-227 |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs | All cycles: Healthy liver | 1.01 percentage of injected 177Lu-3BP-227 |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs | All cycles: Spleen | 0.280 percentage of injected 177Lu-3BP-227 |
Secondary
Phase 1: Metabolic Tumor Response Using Positron Emission Tomography (PET) Response Criteria In Solid Tumors (PERCIST) Version 1.0 or Practical PERCIST
Tumor response assessments were planned to perform by the site investigator (local) for the phase 1 and dose escalation part and by independent reader (central) for the phase 2. All fluorine-18 fluorodeoxyglucose-PET images were used for the metabolic tumor response assessments as described in PERCIST version 1.0 by the Investigator and/or independent readers.
Time frame: From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
Population: Due to the early termination of the study, metabolic tumor response was not collected.
Secondary
Phase 1: Number of Participants With Disease Control Rate (DCR)
The DCR was defined as number of participants with a BOR characterized as CR, PR or stable disease according to RECIST 1.1 relative to the total number of evaluable participants.
Time frame: From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
Population: Primary Pharmacodynamic population (for tumor response) included all participants who received at least 2 therapeutic doses of 177Lu-3BP-227 and reached the end of Cycle 2 or EOCT visit with available post-baseline tumor assessment based on RECIST 1.1 and with no major protocol deviations with an impact on the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Disease Control Rate (DCR) | 0 Participants |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Number of Participants With Disease Control Rate (DCR) | 1 Participants |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Number of Participants With Disease Control Rate (DCR) | 0 Participants |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Number of Participants With Disease Control Rate (DCR) | 0 Participants |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Number of Participants With Disease Control Rate (DCR) | 0 Participants |
Secondary
Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ
The absorbed dose to the target lesions and discernible organs (i.e., organs showing uptake) was evaluated by image-based analysis. The organs considered for 177Lu-3BP-227 image-based dosimetry assessment included: healthy liver, total liver, bone marrow, left kidney, right kidney, intestine (large and small), spleen, pancreas, stomach wall, right ovary, left ovary, uterus, right testis, left testis, thymus, right thyroid gland, left thyroid gland, prostate gland and total body. The organ that had the highest absorbed dose of treatment for each participant in each treatment cycle was determined.
Time frame: From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
Population: Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis. Since the study drug administered to the different groups had the same composition/specific activity, no difference in drug distribution was expected between groups and results were reported combining all groups.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 1 | Right kidney | 4 Participants |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 1 | Left kidney | 3 Participants |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 1 | Large intestine | 5 Participants |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 1 | Bladder | 2 Participants |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 1 | Lymph node | 0 Participants |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 2 | Right kidney | 2 Participants |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 2 | Left kidney | 2 Participants |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 2 | Large intestine | 4 Participants |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 2 | Bladder | 2 Participants |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ | Cycle 2 | Lymph node | 1 Participants |
Secondary
Phase 1: Number of Participants With Objective Response Rate (ORR)
The ORR was defined as number of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) relative to the total number of evaluable participants.
Time frame: From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
Population: Primary Pharmacodynamic population (for tumor response) included all participants who received at least 2 therapeutic doses of 177Lu-3BP-227 and reached the end of Cycle 2 or EOCT visit with available post-baseline tumor assessment based on RECIST 1.1 and with no major protocol deviations with an impact on the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Number of Participants With Objective Response Rate (ORR) | 0 Participants |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Number of Participants With Objective Response Rate (ORR) | 1 Participants |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Number of Participants With Objective Response Rate (ORR) | 0 Participants |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Number of Participants With Objective Response Rate (ORR) | 0 Participants |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Number of Participants With Objective Response Rate (ORR) | 0 Participants |
Secondary
Phase 1: Overall Survival (OS)
The OS was defined from first study medication administration until death, according to RECIST 1.1.
Time frame: From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
Population: Due to the early termination of the study, survival analysis on OS was not collected.
Secondary
Phase 1: Progression-Free Survival (PFS)
The PFS was defined as the time from date of first study medication administration until progression, according to RECIST 1.1.
Time frame: From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
Population: Due to the early termination of the study, survival analysis on PFS was not collected.
Secondary
Phase 1: Renal Clearance of 3BP-227 From Plasma
The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227
The specific absorbed dose per organ was evaluated by image-based analysis. The specific absorbed dose (Gray/GBq) was calculated as the absorbed dose to an organ (in Gray) divided by the activity of 177Lu-3BP-227 administered (in GBq).
Time frame: From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
Population: Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis. Since study drug administered to different groups had same composition/specific activity and since the specific absorbed dose is expressed relatively to the administered activity (Gray/Gbq), no difference in specific absorbed dose was expected between groups and results were reported combining all groups.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227 | All cycles: Right kidney | 0.242 Gray/GBq |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227 | All cycles: Bone marrow | 0.0636 Gray/GBq |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227 | All cycles: Healthy liver | 0.0515 Gray/GBq |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227 | All cycles: Left kidney | 0.255 Gray/GBq |
Secondary
Phase 1: Specific Absorbed Dose to the Target Lesions of 177Lu-3BP-227
The specific absorbed dose to the target lesions was evaluated by image-based analysis. Results for all studied diseases (pancreatic ductal adenocarcinoma and colorectal carcinoma) at all anatomical locations (cervical, intrapelvic, liver, lung, lymph node, and pancreas) for all cycles (Cycle 1 and 2) are reported. The specific absorbed dose (Gray/GBq) was calculated as the absorbed dose to the target lesions (in Gray) divided by the activity of 177Lu-3BP-227 administered (in GBq).
Time frame: From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.
Population: Dosimetry population included all participants with organ dosimetry data and with no major protocol deviations with an impact on dosimetry analysis. Since study drug administered to different groups had same composition/specific activity and since the specific absorbed dose is expressed relatively to the administered activity (Gray/Gbq), no difference in specific absorbed dose was expected between groups and results were reported combining all groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Specific Absorbed Dose to the Target Lesions of 177Lu-3BP-227 | 0.183 Gray/GBq |
Secondary
Phase 1: t1/2 of 3BP-227
The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: Time Post Injection to Achieve Cmax of 177Lu-3BP-227
The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.
Population: Due to the early termination of the study, the PK analysis data was not collected.
Secondary
Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9
Changes in tumor markers in serum relevant and specific to the underlying tumor disease was determined.
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal
Population: Pharmacodynamic population included all participants who received at least 1 therapeutic dose and with available post-baseline pharmacodynamics/efficacy data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | EOCT | 112.00 international units/milliliter | — |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 1 Day 1 | 50019.00 international units/milliliter | Standard Deviation 70683.81 |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 2 Day 1 | 66.00 international units/milliliter | — |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 2 Day 1 | 456.33 international units/milliliter | Standard Deviation 753.23 |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 1 Day 1 | 13.00 international units/milliliter | — |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | EOCT | 928.00 international units/milliliter | Standard Deviation 1294.01 |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | EOCT | 1166.90 international units/milliliter | — |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 2 Day 1 | 277.90 international units/milliliter | Standard Deviation 239.71 |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 1 Day 1 | 20939.54 international units/milliliter | Standard Deviation 46482.66 |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Early Withdrawal | 64.90 international units/milliliter | Standard Deviation 86.41 |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Early Withdrawal | 8398.00 international units/milliliter | — |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 1 Day 1 | 1455.50 international units/milliliter | Standard Deviation 78.49 |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 2 Day 1 | 18420.33 international units/milliliter | Standard Deviation 27442.99 |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | EOCT | 3532.00 international units/milliliter | — |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | EOCT | 629.90 international units/milliliter | — |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 2 Day 1 | 490.50 international units/milliliter | — |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 | Cycle 1 Day 1 | 314.70 international units/milliliter | — |
Secondary
Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen
Changes in tumor markers in serum relevant and specific to the underlying tumor disease was determined.
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal
Population: Pharmacodynamic population included all participants who received at least 1 therapeutic dose and with available post-baseline pharmacodynamics/efficacy data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | EOCT | 4.30 microgram per liter | — |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 1 Day 1 | 857.95 microgram per liter | Standard Deviation 1209.22 |
| Cohort 1: 177Lu-3BP-227 2.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 2 Day 1 | 3.20 microgram per liter | — |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 2 Day 1 | 37.93 microgram per liter | Standard Deviation 41.01 |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 1 Day 1 | 117.40 microgram per liter | — |
| Cohort 2: 177Lu-3BP-227 4.0 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | EOCT | 75.50 microgram per liter | Standard Deviation 47.09 |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | EOCT | 321.20 microgram per liter | — |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 2 Day 1 | 210.97 microgram per liter | Standard Deviation 213.86 |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 1 Day 1 | 112.38 microgram per liter | Standard Deviation 94.41 |
| Cohort 3: 177Lu-3BP-227 5.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Early Withdrawal | 53.75 microgram per liter | Standard Deviation 23.83 |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Early Withdrawal | 29.60 microgram per liter | — |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 1 Day 1 | 6.65 microgram per liter | Standard Deviation 7.14 |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 2 Day 1 | 47.87 microgram per liter | Standard Deviation 62.85 |
| Cohort 4: 177Lu-3BP-227 6.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | EOCT | 184.00 microgram per liter | — |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | EOCT | 5.10 microgram per liter | — |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 2 Day 1 | 4.60 microgram per liter | — |
| Cohort 5: 177Lu-3BP-227 7.5 GBq | Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen | Cycle 1 Day 1 | 3.50 microgram per liter | — |
Secondary
Phase 1: Volume of Distribution of 3BP-227
The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Time frame: Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.
Population: Due to the early termination of the study, the PK analysis data was not collected.