Advanced Solid Tumor Malignancy
Conditions
Brief summary
A Phase 1/2a, open-label, dose-escalation study with enrollment in Phase 1 to continue until determination of the Maximum Tolerated Dose (MTD) /Recommended Phase 2a Dose (RP2D), and then enrollment into Phase 2a expansion cohorts will be initiated.
Detailed description
Phase 1 is an open-label, dose-escalation protocol. It is anticipated that up to 36 patients will be enrolled in Phase 1. All patients will be assigned to treatment with CRLX301 as the single agent. For the first 2 cohorts a 1+5 study design will be utilized. A single patient will be enrolled sequentially into cohort 1 and cohort 2. If either patient in cohort 1 or 2 experiences a dose limiting toxicity (DLT) during Cycle 1, then the cohort will be expanded to enroll additional patients up to a total of 6. As of cohort 3 and for all subsequent cohorts, a 3+3 dose escalation schema will be utilized. MTD/RP2D will be determined at the dose level when \<2 of 6 patients experience a DLT in a cohort. The Phase 2a part of the study will be an open-label expansion cohort study. An additional 24 patients with advanced, histologically confirmed solid tumor malignancies will be enrolled. All patients will be assigned to treatment at the MTD/RP2D with CRLX301 as the single agent. All patients will be followed for safety, tumor response, and progression free survival (PFS) all per RECIST version 1.1 guidelines. Patients will remain on study treatment until they experience progression of disease, unacceptable toxicity, or other specified reason for discontinuation.
Interventions
DRUGCRLX301
Sponsors
NewLink Genetics Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1 dose escalation study followed by phase 2a expansion cohort
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥18 years of age 2. Diagnosis of histologically or cytologically confirmed, advanced solid tumor malignancy that is refractory to or not a candidate for standard therapy 3. ECOG 0 or 1 4. Life expectancy \>12 weeks 5. Fertile males or females of childbearing potential agree to use adequate contraception prior to study entry 6. Negative urine pregnancy test
Exclusion criteria
1. Uncontrolled grade 2 or greater toxicity except alopecia 2. Prolongation of QT/QTc interval 3. Women who are pregnant or nursing 4. Any known HIV infection or AIDS or any concurrent infection requiring IV antibiotics 5. Any chronic or concurrent acute liver disease, including viral hepatitis 6. Primary brain malignant tumors 7. Known metastases to the brain 8. Uncontrolled hypertension 9. Concurrent participation in any other investigational study 10. Concurrent treatment with anticoagulation medication, unless approved by Sponsor 11. History of stroke, deep venous thrombosis (DVT), or transient ischemic attack (TIA) 12. History of other cancer type, except for cutaneous basal cell or squamous cell carcinoma, or cervical or prostate cancer in situ, within the last 2 years prior to C1D1 13. Uncontrolled concurrent disease or illness 14. History of severe hypersensitivity reaction to taxanes 15. Peripheral neuropathy exclusions 16. Other condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | 13 to 19 months | Determination of MTD is dependent upon number of dose limiting toxicities and significant adverse events observed. |
| Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability | 12 months | Safety variables will include AEs, SAEs, Severe AEs, Related AEs and AEs leading to Discontinuation in phase 2a subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 2.5 years | Area under the concentration vs time curve of released docetaxel in blood and/or urine specimens of patients receiving at least 1 dose of CRLX301. |
| Percentage of Participants Stratified by Best Overall Tumor Response | 2.5 years | Best overall tumor response will be provided per dose cohort using RECIST 1.1 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Schedule 1 Cohort 1 CRLX301 7.5 mg/m2 IV given every 3 weeks
CRLX301 | 1 |
| Schedule 1 Cohort 2 CRLX301 15 mg/m2 IV given every 3 weeks
CRLX301 | 1 |
| Schedule 1 Cohort 3 CRLX301 30 mg/m2 IV given every 3 weeks
CRLX301 | 3 |
| Schedule 1 Cohort 5 CRLX301 60 mg/m2 IV given every 3 weeks
CRLX301 | 3 |
| Schedule 1 Cohort 6 CRLX301 75 mg/m2 IV given every 3 weeks
CRLX301 | 6 |
| Schedule 1 Cohort 7 CRLX301 90 mg/m2 IV given every 3 weeks
CRLX301 | 6 |
| Schedule 2 Cohort 1 CRLX301 25 mg/m2 IV given weekly
CRLX301 | 3 |
| Schedule 2 Cohort 2 CRLX301 35 mg/m2 IV given weekly
CRLX301 | 4 |
| Schedule 2 Cohort 3 CRLX301 45 mg/m2 IV given weekly
CRLX301 | 4 |
| Schedule 2 Cohort 4 CRLX301 54 mg/m2 IV given weekly
CRLX301 | 2 |
| Schedule 2 Cohort 5 CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off
CRLX301 | 4 |
| Phase 2a Expansion Cohort CRLX301 75mg/m2 IV given every 3 weeks
CRLX301 | 5 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 1 | 4 | 2 | 2 | 2 | 1 | 2 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 | 2 | 0 | 4 | 1 | 1 | 2 | 2 | 0 | 2 | 1 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Schedule 2 Cohort 5 | Phase 2a Expansion Cohort | Total | Schedule 2 Cohort 2 | Schedule 2 Cohort 1 | Schedule 1 Cohort 7 | Schedule 1 Cohort 6 | Schedule 1 Cohort 5 | Schedule 1 Cohort 3 | Schedule 1 Cohort 2 | Schedule 1 Cohort 1 | Schedule 2 Cohort 4 | Schedule 2 Cohort 3 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 3.1 | 66.8 years STANDARD_DEVIATION 4.15 | 61.8 years STANDARD_DEVIATION 10.2 | 56 years STANDARD_DEVIATION 11.52 | 65 years STANDARD_DEVIATION 2.65 | 60.2 years STANDARD_DEVIATION 11.62 | 63.8 years STANDARD_DEVIATION 9.79 | 67.3 years STANDARD_DEVIATION 1.53 | 59 years STANDARD_DEVIATION 19 | 43 years | 74 years | 72.5 years STANDARD_DEVIATION 2.12 | 54 years STANDARD_DEVIATION 12.25 |
| Baseline BMI (kg/m^2) | 26.758 kg/m^2 STANDARD_DEVIATION 4.967 | 29.118 kg/m^2 STANDARD_DEVIATION 8.0521 | 27.783 kg/m^2 STANDARD_DEVIATION 3.2805 | 25.173 kg/m^2 STANDARD_DEVIATION 5.7256 | 33.869 kg/m^2 STANDARD_DEVIATION 5.5301 | 27.422 kg/m^2 STANDARD_DEVIATION 2.781 | 26.779 kg/m^2 STANDARD_DEVIATION 4.8762 | 26.917 kg/m^2 STANDARD_DEVIATION 7.6956 | 28.023 kg/m^2 STANDARD_DEVIATION 1.2871 | 19.63 kg/m^2 | 30.255 kg/m^2 | 28.142 kg/m^2 STANDARD_DEVIATION 3.4551 | 24.340 kg/m^2 STANDARD_DEVIATION 3.1519 |
| Baseline ECOG Status ECOG PS Score 0 | 1 Participants | 1 Participants | 17 Participants | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Baseline ECOG Status ECOG PS Score 1 | 3 Participants | 4 Participants | 25 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 38 Participants | 4 Participants | 3 Participants | 6 Participants | 6 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 3 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Primary Site of Disease at Study Entry Abdomen/peritoneum | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Site of Disease at Study Entry Bladder | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Site of Disease at Study Entry Bone | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Primary Site of Disease at Study Entry Breast | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Site of Disease at Study Entry Hepatic/liver | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Primary Site of Disease at Study Entry Lung | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Primary Site of Disease at Study Entry Lymph nodes | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Primary Site of Disease at Study Entry Other (not specified) | 3 Participants | 1 Participants | 18 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Site of Disease at Study Entry Pancreas | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Primary Site of Disease at Study Entry Pleura | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Primary Site of Disease at Study Entry Prostate | 1 Participants | 3 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Primary Site of Disease at Study Entry Skin | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 37 Participants | 3 Participants | 3 Participants | 4 Participants | 6 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 16 Participants | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 26 Participants | 3 Participants | 0 Participants | 2 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 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 | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 1 / 1 | 1 / 3 | 1 / 3 | 0 / 6 | 0 / 6 | 0 / 3 | 2 / 4 | 0 / 4 | 0 / 2 | 0 / 4 | 1 / 5 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 3 / 3 | 3 / 3 | 6 / 6 | 6 / 6 | 3 / 3 | 4 / 4 | 4 / 4 | 2 / 2 | 4 / 4 | 5 / 5 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 | 3 / 3 | 3 / 3 | 1 / 6 | 3 / 6 | 1 / 3 | 2 / 4 | 1 / 4 | 1 / 2 | 0 / 4 | 2 / 5 |
Outcome results
Primary
Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities
Determination of MTD is dependent upon number of dose limiting toxicities and significant adverse events observed.
Time frame: 13 to 19 months
Population: The phase 1 safety population were analyzed for dose limiting toxicities and treatment emergent adverse events. Treatment totals include all patients that received the specific dose at any point during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Schedule 1 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 1 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 0 Patients with event |
| Schedule 1 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 0 Patients with event |
| Schedule 1 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 1 Patients with event |
| Schedule 1 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 1 Patients with event |
| Schedule 1 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 0 Patients with event |
| Schedule 1 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 1 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 1 Patients with event |
| Schedule 1 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 1 Patients with event |
| Schedule 1 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 0 Patients with event |
| Schedule 1 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 1 Patients with event |
| Schedule 1 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 1 Patients with event |
| Schedule 1 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 3 Patients with event |
| Schedule 1 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 3 Patients with event |
| Schedule 1 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 2 Patients with event |
| Schedule 1 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 1 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 0 Patients with event |
| Schedule 1 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 3 Patients with event |
| Schedule 1 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 2 Patients with event |
| Schedule 1 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 3 Patients with event |
| Schedule 1 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 3 Patients with event |
| Schedule 1 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 3 Patients with event |
| Schedule 1 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 3 Patients with event |
| Schedule 1 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 1 Cohort 6 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 4 Patients with event |
| Schedule 1 Cohort 6 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 6 Patients with event |
| Schedule 1 Cohort 6 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 1 Patients with event |
| Schedule 1 Cohort 6 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 1 Patients with event |
| Schedule 1 Cohort 6 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 6 Patients with event |
| Schedule 1 Cohort 6 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 1 Cohort 7 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 6 Patients with event |
| Schedule 1 Cohort 7 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 6 Patients with event |
| Schedule 1 Cohort 7 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 3 Patients with event |
| Schedule 1 Cohort 7 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 2 Patients with event |
| Schedule 1 Cohort 7 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 6 Patients with event |
| Schedule 1 Cohort 7 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 4 Patients with event |
| Schedule 2 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 2 Patients with event |
| Schedule 2 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 3 Patients with event |
| Schedule 2 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 2 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 0 Patients with event |
| Schedule 2 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 1 Patients with event |
| Schedule 2 Cohort 1 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 3 Patients with event |
| Schedule 2 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 1 Patients with event |
| Schedule 2 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 2 Patients with event |
| Schedule 2 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 2 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 4 Patients with event |
| Schedule 2 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 3 Patients with event |
| Schedule 2 Cohort 2 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 2 Patients with event |
| Schedule 2 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 2 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 2 Patients with event |
| Schedule 2 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 1 Patients with event |
| Schedule 2 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 4 Patients with event |
| Schedule 2 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 4 Patients with event |
| Schedule 2 Cohort 3 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 2 Patients with event |
| Schedule 2 Cohort 4 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 2 Patients with event |
| Schedule 2 Cohort 4 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 2 Patients with event |
| Schedule 2 Cohort 4 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 1 Patients with event |
| Schedule 2 Cohort 4 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 1 Patients with event |
| Schedule 2 Cohort 4 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 2 Cohort 4 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 2 Patients with event |
| Schedule 2 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE leading to discontinuation | 0 Patients with event |
| Schedule 2 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one TEAE | 4 Patients with event |
| Schedule 2 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one DLT | 0 Patients with event |
| Schedule 2 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one Serious TEAE | 0 Patients with event |
| Schedule 2 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one severe TEAE | 4 Patients with event |
| Schedule 2 Cohort 5 | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | At least one related TEAE | 4 Patients with event |
Primary
Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability
Safety variables will include AEs, SAEs, Severe AEs, Related AEs and AEs leading to Discontinuation in phase 2a subjects.
Time frame: 12 months
Population: The safety population (all patients) were analyzed for dose limiting toxicities and treatment emergent adverse events. Treatment totals include all patients that received the specific dose at any point during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Schedule 1 Cohort 1 | Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability | At least one TEAE | 5 Patients with event |
| Schedule 1 Cohort 1 | Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability | At least one Serious TEAE | 2 Patients with event |
| Schedule 1 Cohort 1 | Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability | At least one severe TEAE | 5 Patients with event |
| Schedule 1 Cohort 1 | Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability | At least one related TEAE | 5 Patients with event |
| Schedule 1 Cohort 1 | Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability | At least one TEAE leading to discontinuation | 2 Patients with event |
Secondary
Evaluate the Pharmacokinetic (PK) Profile of CRLX301
Area under the concentration vs time curve of released docetaxel in blood and/or urine specimens of patients receiving at least 1 dose of CRLX301.
Time frame: 2.5 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule 1 Cohort 1 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 295 ng/ml*h | Standard Deviation 0 |
| Schedule 1 Cohort 2 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 2197 ng/ml*h | Standard Deviation 0 |
| Schedule 1 Cohort 3 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 1695 ng/ml*h | Standard Deviation 438 |
| Schedule 1 Cohort 5 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 3783 ng/ml*h | Standard Deviation 1054 |
| Schedule 1 Cohort 6 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 3613 ng/ml*h | Standard Deviation 1054 |
| Schedule 1 Cohort 7 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 4639 ng/ml*h | Standard Deviation 1561 |
| Schedule 2 Cohort 1 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 1433 ng/ml*h | Standard Deviation 154 |
| Schedule 2 Cohort 2 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 2205 ng/ml*h | Standard Deviation 731 |
| Schedule 2 Cohort 3 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 2019 ng/ml*h | Standard Deviation 325 |
| Schedule 2 Cohort 4 | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 2350 ng/ml*h | Standard Deviation 453 |
Secondary
Percentage of Participants Stratified by Best Overall Tumor Response
Best overall tumor response will be provided per dose cohort using RECIST 1.1
Time frame: 2.5 years
Population: All patients treated on study (safety population) were evaluated for overall tumor response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Schedule 1 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 1 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Schedule 1 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 0 percentage of participants |
| Schedule 1 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 100 percentage of participants |
| Schedule 1 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 1 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Schedule 1 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 0 percentage of participants |
| Schedule 1 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 1 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 1 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 100 percentage of participants |
| Schedule 1 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 1 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Schedule 1 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 33.3 percentage of participants |
| Schedule 1 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 1 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 66.7 percentage of participants |
| Schedule 1 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 1 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 1 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 0 percentage of participants |
| Schedule 1 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 100 percentage of participants |
| Schedule 1 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Schedule 1 Cohort 6 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 16.7 percentage of participants |
| Schedule 1 Cohort 6 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Schedule 1 Cohort 6 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 66.7 percentage of participants |
| Schedule 1 Cohort 6 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 1 Cohort 6 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 1 Cohort 7 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 1 Cohort 7 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 16.7 percentage of participants |
| Schedule 1 Cohort 7 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 16.7 percentage of participants |
| Schedule 1 Cohort 7 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 1 Cohort 7 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Schedule 2 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Schedule 2 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 0 percentage of participants |
| Schedule 2 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 2 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 100 percentage of participants |
| Schedule 2 Cohort 1 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 2 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 25 percentage of participants |
| Schedule 2 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 2 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Schedule 2 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 75 percentage of participants |
| Schedule 2 Cohort 2 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 2 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 25 percentage of participants |
| Schedule 2 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 25 percentage of participants |
| Schedule 2 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 50 percentage of participants |
| Schedule 2 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 2 Cohort 3 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 2 Cohort 4 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 50 percentage of participants |
| Schedule 2 Cohort 4 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 2 Cohort 4 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Schedule 2 Cohort 4 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 2 Cohort 4 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 50 percentage of participants |
| Schedule 2 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 0 percentage of participants |
| Schedule 2 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Schedule 2 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Schedule 2 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 100 percentage of participants |
| Schedule 2 Cohort 5 | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 0 percentage of participants |
| Phase 2a Expansion Cohort | Percentage of Participants Stratified by Best Overall Tumor Response | Not Evaluated | 0 percentage of participants |
| Phase 2a Expansion Cohort | Percentage of Participants Stratified by Best Overall Tumor Response | Complete Response | 0 percentage of participants |
| Phase 2a Expansion Cohort | Percentage of Participants Stratified by Best Overall Tumor Response | Progressive Disease | 20 percentage of participants |
| Phase 2a Expansion Cohort | Percentage of Participants Stratified by Best Overall Tumor Response | Partial Response | 20 percentage of participants |
| Phase 2a Expansion Cohort | Percentage of Participants Stratified by Best Overall Tumor Response | Stable Disease | 40 percentage of participants |