Prostate Cancer
Conditions
Keywords
prostate cancer, metastatic castration resistant prostate cancer, prostate specific membrane antigen, mCRPC, PSMA, positron emission tomography, PET, radiotherapy, targeted therapy, lutetium, 177Lu
Brief summary
The purpose of this study is to find the highest dose level of study drug, CTT1403, that can be safely administered to patients with metastatic castration resistant prostate cancer (mCRPC).
Detailed description
This is a Phase 1, first-in-human dose escalation/dose expansion study evaluating escalating doses of CTT1403 in patients with PSMA-avid mCRPC with progressive disease on at least one androgen signaling inhibitor, followed by a dose expansion to further evaluate the safety, tolerability, efficacy and biological activity of CTT1403. CTT1403 is a PSMA-targeted 177Lu-labeled radiotherapy being developed for prostate cancer with a unique PSMA binding scaffold and an albumin binding moiety to extend circulation half-life. The PSMA binding scaffold is shared with CTT1057, a PSMA-specific PET diagnostic imaging agent shown in Phase 1 clinical trials to be specifically taken up by PSMA+ tumor. PSMA PET imaging by CTT1057 will be used diagnostically to select patients with PSMA-avid disease for treatment. The purpose of this study is to identify the dose limiting toxicity and recommended phase 2 dose of CTT1403. Eligible participants with demonstrated therapeutic benefit will be offered a second dose of study drug.
Interventions
DRUGCTT1403
Escalating doses of 0.75 GBq - 9.0 GBq will be administered in an accelerated to traditional 3+3 dose escalation design. After escalation, 10 additional patients will be enrolled into a dose expansion cohort. Patients meeting eligibility criteria with demonstrated cessation of disease progression will be offered a second dose of the study drug, CTT1403.
DRUGCTT1057
Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.
DRUG68Ga-PSMA-11
Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.
Sponsors
University of California, San Francisco
National Cancer Institute (NCI)
Cancer Targeted Technology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically confirmed prostate adenocarcinoma that is metastatic and castration resistant (mCRPC). * At least 3 metastatic foci avid for PSMA-specific PET agent (CTT1057) uptake on Screening PSMA PET. * Has received docetaxol, ineligible for docetaxol, or refused docetaxol for the treatment of prostate cancer. * Has progression by the PCWG3 criteria during or after treatment with either abiraterone or enzalutamide * Male Age ≥ 18 years. * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 2). * Demonstrate adequate organ function
Exclusion criteria
* Has received previous treatment with radium-223 or another radiopharmaceutical within 3 months prior to first dose of CTT1403. * Has received prior systemic anti-cancer therapy (excluding radiopharmaceutical) within 14 days, or 5 half-lives, whichever is shorter, prior to first dose of CTT1403. * Has received external-beam radiation within 14 days prior to first dose of CTT1403. * Has received cabazitaxel for the treatment of mCRPC. * Has received previous treatment with a therapeutic targeting PSMA. * Has an additional active malignancy requiring therapy that may confound the assessment of the study endpoints. * Has clinically significant cardiovascular disease * Has a history of untreated brain metastases * Has evidence of diffuse bone marrow involvement by prostate cancer in the judgment of study investigator. * Clinically significant urinary obstruction or moderate/severe hydronephrosis on baseline imaging. * Has a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days before CTT1403 administration. * Has known positive status for chronic hepatitis B or hepatitis C * Known or suspected myelodysplastic syndrome. * Has any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | 6-8 weeks from time of injection on Cycle 1 - Day 1 | The dose-limiting toxicity was defined as any of the following: 1. Grade 4 neutropenia lasting \> 5 consecutive days 2. Grade 3 or 4 febrile neutropenia 3. Grade 4 thrombocytopenia lasting ≥ 7 days, or Grade 3 or 4 thrombocytopenia with clinically significant bleeding or requirement for platelet transfusion 4. Any nonhematologic, treatment-related AE ≥ Grade 3, with the exceptions of Grade 3 nausea, vomiting, diarrhea, non-clinically significant electrolyte abnormality, constipation, fever, fatigue, or skin rash that resolves to Grade ≤ 2 within 72 hours with optimal medical management 5. Any other treatment-related toxicity that results in delay of Cycle 2 administration of CTT1403 by \> 21 days and/or toxicity considered by the Investigator and Sponsor's medical representatives to be dose-limiting. |
| Objective Response Rate by RECIST v1.1 Criteria | Cycle 1-Day 35, Cycle 2-Day 35, 30 Days After Last Dose, 8 Weeks Post-Treatment. Each cycle lasted 35 days. | Changes in only the largest diameters (unidimensional measurment) of the tumor lesions are used in the RECIST v1.1 criteria. Data presented as RECIST Overall Response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | 2 hrs ± 1 followed by 24±12 hrs, 48±12 hrs, and 168±24 hrs post-infusion on Cycle 1-Day 1 | Organ dosimetry was assessed via SPECT/CT imaging until two imaging periods have been collected in which study drug cannot be detected by SPECT/CT. Time points included (2 hrs ± 1 followed by 24±12 hrs, 48±12 hrs, and 168±24 hrs post-infusion on Cycle 1-Day 1. Data calculated using OLINDA. Absorbed dose is calculated as single value wherein absorbed dose is proportional to the integral of activity over time. |
| Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Cycle 1-Day 1 and Cycle 2-Day 1. Each cycle lasted 35 days. | The Brief Pain Index uses a scale of 0-10 to rate the severity of pain. A rating of 0 indicates no pain. A rating of 10 indicates the worst pain imaginable. |
| Assessment of Pharmacokinetics of CTT1403 | Samples were collected during Cycle 1 (timepoints start at the initiation of infusion): Day 1 (30 min +/- 5 min and 2 hrs +/- 30 min), Day 2 (24 hrs +/- 12 hrs), Day 3 (48 hrs +/- 12 hrs), Day 8 (168 hrs +/- 24 hrs), Day 15 (336 hrs +/- 24 hrs) | The distribution half-life and the elimination half-life of CTT1403 were calculated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.75 GBq Cohort 0.75 GBq dose of CTT1403 | 1 |
| 1.5 GBq Cohort 1.5 GBq dose of CTT1403 | 1 |
| 2.0 GBq Cohort 2.0GBq dose of CTT1403 | 1 |
| 3.0 GBq Cohort 3.0 GBq dose of CTT1403 | 3 |
| 4.5 GBq Cohort 4.5 GBq dose of CTT1403 | 4 |
| 6.0 GBq Cohort 6.0 GBq dose of CTT1403 | 3 |
| 7.5 GBq Cohort 7.5 GBq dose of CTT1403 | 3 |
| 9.0 GBq Cohort 9.0 GBq dose of CTT1403 | 1 |
| Total | 17 |
Baseline characteristics
| Characteristic | 0.75 GBq Cohort | Total | 9.0 GBq Cohort | 7.5 GBq Cohort | 6.0 GBq Cohort | 4.5 GBq Cohort | 3.0 GBq Cohort | 2.0 GBq Cohort | 1.5 GBq Cohort |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 83 years | 73.41 years STANDARD_DEVIATION 7.37 | 74 years | 82 years STANDARD_DEVIATION 1 | 72 years STANDARD_DEVIATION 7.81 | 70 years STANDARD_DEVIATION 2.58 | 65 years STANDARD_DEVIATION 7.55 | 79 years | 75 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 16 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 15 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 17 participants | 1 participants | 3 participants | 3 participants | 4 participants | 3 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 17 Participants | 1 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 1 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 1 | 1 / 1 | 3 / 3 | 4 / 4 | 3 / 3 | 3 / 3 | 1 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 0 / 1 | 2 / 3 | 2 / 4 | 2 / 3 | 1 / 3 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 3 | 1 / 4 | 1 / 3 | 1 / 3 | 0 / 1 |
Outcome results
Primary
Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403
The dose-limiting toxicity was defined as any of the following: 1. Grade 4 neutropenia lasting \> 5 consecutive days 2. Grade 3 or 4 febrile neutropenia 3. Grade 4 thrombocytopenia lasting ≥ 7 days, or Grade 3 or 4 thrombocytopenia with clinically significant bleeding or requirement for platelet transfusion 4. Any nonhematologic, treatment-related AE ≥ Grade 3, with the exceptions of Grade 3 nausea, vomiting, diarrhea, non-clinically significant electrolyte abnormality, constipation, fever, fatigue, or skin rash that resolves to Grade ≤ 2 within 72 hours with optimal medical management 5. Any other treatment-related toxicity that results in delay of Cycle 2 administration of CTT1403 by \> 21 days and/or toxicity considered by the Investigator and Sponsor's medical representatives to be dose-limiting.
Time frame: 6-8 weeks from time of injection on Cycle 1 - Day 1
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.75 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who experienced a dose-limiting toxicity | 0 Participants |
| 0.75 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who did not experience a dose-limiting toxicity | 1 Participants |
| 1.5 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who experienced a dose-limiting toxicity | 0 Participants |
| 1.5 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who did not experience a dose-limiting toxicity | 1 Participants |
| 2.0 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who experienced a dose-limiting toxicity | 0 Participants |
| 2.0 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who did not experience a dose-limiting toxicity | 1 Participants |
| 3.0 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who experienced a dose-limiting toxicity | 0 Participants |
| 3.0 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who did not experience a dose-limiting toxicity | 3 Participants |
| 4.5 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who experienced a dose-limiting toxicity | 0 Participants |
| 4.5 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who did not experience a dose-limiting toxicity | 4 Participants |
| 6.0 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who experienced a dose-limiting toxicity | 0 Participants |
| 6.0 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who did not experience a dose-limiting toxicity | 3 Participants |
| 7.5 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who did not experience a dose-limiting toxicity | 3 Participants |
| 7.5 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who experienced a dose-limiting toxicity | 0 Participants |
| 9.0 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who experienced a dose-limiting toxicity | 0 Participants |
| 9.0 GBq Cohort | Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403 | Number of participants who did not experience a dose-limiting toxicity | 1 Participants |
Primary
Objective Response Rate by RECIST v1.1 Criteria
Changes in only the largest diameters (unidimensional measurment) of the tumor lesions are used in the RECIST v1.1 criteria. Data presented as RECIST Overall Response.
Time frame: Cycle 1-Day 35, Cycle 2-Day 35, 30 Days After Last Dose, 8 Weeks Post-Treatment. Each cycle lasted 35 days.
Population: In cases where the number analyzed differs from the total number in the group, data was either not available, patient was lost to follow-up, or patient withdrew.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.75 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 30 days after last dose | 0 Participants |
| 0.75 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 1-Day 35 | 0 Participants |
| 0.75 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 1-Day 35 | 0 Participants |
| 0.75 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 2-Day 35 | 0 Participants |
| 0.75 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 8 weeks post-treatment | 0 Participants |
| 0.75 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 2-Day 35 | 0 Participants |
| 0.75 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 30 days after last dose | 0 Participants |
| 0.75 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 8 weeks post-treatment | 0 Participants |
| 1.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 2-Day 35 | 0 Participants |
| 1.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 8 weeks post-treatment | 0 Participants |
| 1.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 8 weeks post-treatment | 0 Participants |
| 1.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 1-Day 35 | 1 Participants |
| 1.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 2-Day 35 | 1 Participants |
| 1.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 30 days after last dose | 0 Participants |
| 1.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 1-Day 35 | 0 Participants |
| 1.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 30 days after last dose | 0 Participants |
| 2.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 30 days after last dose | 1 Participants |
| 2.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 8 weeks post-treatment | 0 Participants |
| 2.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 2-Day 35 | 0 Participants |
| 2.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 1-Day 35 | 1 Participants |
| 2.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 1-Day 35 | 0 Participants |
| 2.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 8 weeks post-treatment | 0 Participants |
| 2.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 30 days after last dose | 0 Participants |
| 2.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 2-Day 35 | 0 Participants |
| 3.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 1-Day 35 | 1 Participants |
| 3.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 8 weeks post-treatment | 0 Participants |
| 3.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 1-Day 35 | 2 Participants |
| 3.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 30 days after last dose | 0 Participants |
| 3.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 2-Day 35 | 0 Participants |
| 3.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 8 weeks post-treatment | 0 Participants |
| 3.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 30 days after last dose | 1 Participants |
| 3.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 2-Day 35 | 1 Participants |
| 4.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 30 days after last dose | 0 Participants |
| 4.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 1-Day 35 | 4 Participants |
| 4.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 2-Day 35 | 2 Participants |
| 4.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 1-Day 35 | 0 Participants |
| 4.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 30 days after last dose | 0 Participants |
| 4.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 2-Day 35 | 0 Participants |
| 4.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 8 weeks post-treatment | 1 Participants |
| 4.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 8 weeks post-treatment | 0 Participants |
| 6.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 1-Day 35 | 1 Participants |
| 6.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 1-Day 35 | 2 Participants |
| 6.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 2-Day 35 | 1 Participants |
| 6.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 2-Day 35 | 1 Participants |
| 6.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 30 days after last dose | 0 Participants |
| 6.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 30 days after last dose | 0 Participants |
| 6.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 8 weeks post-treatment | 0 Participants |
| 6.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 8 weeks post-treatment | 1 Participants |
| 7.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 2-Day 35 | 3 Participants |
| 7.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 30 days after last dose | 0 Participants |
| 7.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 1-Day 35 | 1 Participants |
| 7.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 8 weeks post-treatment | 1 Participants |
| 7.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 1-Day 35 | 1 Participants |
| 7.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 8 weeks post-treatment | 0 Participants |
| 7.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 30 days after last dose | 0 Participants |
| 7.5 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 2-Day 35 | 0 Participants |
| 9.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 30 days after last dose | 0 Participants |
| 9.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 2-Day 35 | 1 Participants |
| 9.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 2-Day 35 | 0 Participants |
| 9.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 8 weeks post-treatment | 0 Participants |
| 9.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease on Cycle 1-Day 35 | 0 Participants |
| 9.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease on Cycle 1-Day 35 | 1 Participants |
| 9.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with progressive disease 8 weeks post-treatment | 0 Participants |
| 9.0 GBq Cohort | Objective Response Rate by RECIST v1.1 Criteria | Number of patients with stable disease 30 days after last dose | 0 Participants |
Secondary
Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging
Organ dosimetry was assessed via SPECT/CT imaging until two imaging periods have been collected in which study drug cannot be detected by SPECT/CT. Time points included (2 hrs ± 1 followed by 24±12 hrs, 48±12 hrs, and 168±24 hrs post-infusion on Cycle 1-Day 1. Data calculated using OLINDA. Absorbed dose is calculated as single value wherein absorbed dose is proportional to the integral of activity over time.
Time frame: 2 hrs ± 1 followed by 24±12 hrs, 48±12 hrs, and 168±24 hrs post-infusion on Cycle 1-Day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.75 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Right Kidney | 0593 Gy/GBq | — |
| 0.75 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Left Kidney | 0.608 Gy/GBq | — |
| 1.5 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Left Kidney | 0.611 Gy/GBq | — |
| 1.5 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Right Kidney | 0.585 Gy/GBq | — |
| 2.0 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Left Kidney | 0.760 Gy/GBq | — |
| 2.0 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Right Kidney | 1.021 Gy/GBq | — |
| 3.0 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Right Kidney | 1.032 Gy/GBq | Standard Deviation 0.55 |
| 3.0 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Left Kidney | 1.024 Gy/GBq | Standard Deviation 0.428 |
| 4.5 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Right Kidney | 0.638 Gy/GBq | Standard Deviation 0.108 |
| 4.5 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Left Kidney | 0.579 Gy/GBq | Standard Deviation 0.127 |
| 6.0 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Left Kidney | 0.518 Gy/GBq | Standard Deviation 0.072 |
| 6.0 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Right Kidney | 0.477 Gy/GBq | Standard Deviation 0.064 |
| 7.5 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Left Kidney | 0.774 Gy/GBq | Standard Deviation 0.199 |
| 7.5 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Right Kidney | 0.731 Gy/GBq | Standard Deviation 0.279 |
| 9.0 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Left Kidney | 0.699 Gy/GBq | — |
| 9.0 GBq Cohort | Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging | Mean absorbed dose per GBq - Right Kidney | 0.677 Gy/GBq | — |
Secondary
Assessment of Pharmacokinetics of CTT1403
The distribution half-life and the elimination half-life of CTT1403 were calculated.
Time frame: Samples were collected during Cycle 1 (timepoints start at the initiation of infusion): Day 1 (30 min +/- 5 min and 2 hrs +/- 30 min), Day 2 (24 hrs +/- 12 hrs), Day 3 (48 hrs +/- 12 hrs), Day 8 (168 hrs +/- 24 hrs), Day 15 (336 hrs +/- 24 hrs)
Population: In cases where the number analyzed differs from the total number in the group, data was either not available, patient was lost to follow-up, or patient withdrew.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Distribution half-life | 0.747 hours | — |
| 1.5 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Elimination half-life | 28.881 hours | — |
| 2.0 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Distribution half-life | 1.044 hours | — |
| 2.0 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Elimination half-life | 23.902 hours | — |
| 3.0 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Distribution half-life | 0.699 hours | Standard Deviation 0.267 |
| 3.0 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Elimination half-life | 29.616 hours | Standard Deviation 2.673 |
| 4.5 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Elimination half-life | 36.867 hours | Standard Deviation 4.531 |
| 4.5 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Distribution half-life | 0.813 hours | Standard Deviation 0.068 |
| 6.0 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Distribution half-life | 0.680 hours | Standard Deviation 0.149 |
| 6.0 GBq Cohort | Assessment of Pharmacokinetics of CTT1403 | Elimination half-life | 38.173 hours | Standard Deviation 11.365 |
Secondary
Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index
The Brief Pain Index uses a scale of 0-10 to rate the severity of pain. A rating of 0 indicates no pain. A rating of 10 indicates the worst pain imaginable.
Time frame: Cycle 1-Day 1 and Cycle 2-Day 1. Each cycle lasted 35 days.
Population: In cases where the number analyzed differs from the total number in the group, data was either not available, patient was lost to follow-up, or patient withdrew.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 0.75 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 0.75 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 0.75 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 0.75 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 0.75 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 0.75 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 1.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 1.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 1.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 1.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 1.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 1.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 2.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 2.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 2.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 2.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 2.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 2.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 3.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 1 Participants |
| 3.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 3.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 3.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 1 Participants |
| 3.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 3.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 4.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 4.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 1 Participants |
| 4.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 3 Participants |
| 4.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 1 Participants |
| 4.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 4.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 1 Participants |
| 6.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 1 Participants |
| 6.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 6.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 6.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 1 Participants |
| 6.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 6.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 7.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 7.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 2 Participants |
| 7.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 7.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 2 Participants |
| 7.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 7.5 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 9.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 9.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 9.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced an increase in reported pain | 0 Participants |
| 9.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |
| 9.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of average pain from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced no change in reported pain | 0 Participants |
| 9.0 GBq Cohort | Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index | Change in rating of pain at its worst in the past 24 hours from Cycle 1-Day 1 to Cycle 2-Day 1 | Experienced a decrease in reported pain | 0 Participants |