Company decision

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.

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.

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.

All AEs were collected occurring during the study period from the time of the first dose to the last day of the 30-day post-treatment follow-up period.