Study to Evaluate Maximum Tolerated Dose of Oral CB-03-10 With Dose Expansion Phase, in Advanced Solid Tumors

Study Overview
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Brief Summary
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Subjects will undergo baseline evaluation and an assessment of extent of disease. Subjects in Part 1 (Dose Escalation) will receive escalating doses of CB-03-10 based on a modified Fibonacci schema using a standard oncology 3+3 study design to define an MTD and a RP2D. Plasma PK samples will be collected at predetermined timepoints for all subjects. Subjects in Part 2 (Dose Expansion) of the study will receive CB-03-10 at the RP2D determined in the Part 1 of the study. The indications included in each group will be determined at the completion of Part 1 of the study by Safety Review Committee (SRC). Subjects will be evaluated weekly initially (for 2 cycles in Part 1 and for 1 cycle in Part 2) and every 2 weeks thereafter. Reassessment of disease will be conducted at Week 8 and every 8 weeks thereafter. Subjects with evidence of response (partial or complete) will be re-evaluated at least 4 weeks later for confirmation.

Detailed Description
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Subjects will undergo baseline evaluation and an assessment of extent of disease. Subjects in Part 1 (Dose Escalation) will receive escalating doses of CB-03-10 based on a modified Fibonacci schema using a standard oncology 3+3 study design to define an MTD and a RP2D. Plasma PK samples will be collected at predetermined timepoints for all subjects. Subjects in Part 2 (Dose Expansion) of the study will receive CB-03-10 at the RP2D determined in the Part 1 of the study. The indications included in each group will be determined at the completion of Part 1 of the study by Safety Review Committee (SRC). Subjects will be evaluated weekly initially (for 2 cycles in Part 1 and for 1 cycle in Part 2) and every 2 weeks thereafter. Reassessment of disease will be conducted at Week 8 and every 8 weeks thereafter. Subjects with evidence of response (partial or complete) will be re-evaluated at least 4 weeks later for confirmation.

Official Title
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Open Label, Multicenter, Phase 1 Study to Evaluate the Maximum Tolerated Dose of Orally Administered CB-03-10 With Dose Expansion Phase, in Subjects With Advanced Solid Tumors

Conditions
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Advanced Refractory Solid Tumors, Subjects Considered Likely to Respond to CB-03-10

Intervention / Treatment
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* Drug: CB-03-10


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Signed informed consent For Part 1 (Dose Escalation): Histologically or cytologically confirmed relapsed or refractory locally advanced or metastatic solid tumor, not amenable to standard therapy For Part 2 (Dose Expansion): Histologically or cytologically confirmed relapsed or refractory locally advanced or metastatic solid tumor limited to a specific tumor subtype as determined by the SRC Age >18 years Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 For Part 1 (Dose Escalation): Measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria For Part 2 (Dose Expansion): Measurable disease as per RECIST v1.1 criteria. Adequate renal, hepatic and bone marrow function as defined by Screening labs Negative pregnancy test for females of childbearing potential at the Screening Visit and use of appropriate method of birth control. EXCLUSION CRITERIA Pregnant or breastfeeding women Known central nervous system (CNS) metastases or spinal cord compression Known second cancer of other primary origin (excluding Stage I non-melanoma skin cancer and prostate cancer controlled with hormonal therapy) within the prior 5 years Active autoimmune disease Significant cardiac disease Uncontrolled hypertension Major surgery or irradiation within 28 days prior to start of study treatment Fewer than 28 days (or fewer than 5 half-lives, whichever is shorter) from prior anticancer therapy Requirement for chronic corticosteroids or other immunosuppressant drugs Known infection with hepatitis B or C virus Known infection with HIV and CD4+ T-cell counts < 350 cells/uL Patients with an opportunistic infection within the past 12 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1 (Dose Escalation): Subjects with advanced refractory solid tumors Part 2 (Dose Expansion): Defined subject subgroups considered likely to respond to CB-03-10 (eg, relapsed/refractory pancreatic adenocarcinoma, androgen independent prostate adenocarcinoma, triple-negative breast adenocarcinoma) or indications that demonstrated activity in Part 1
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Part 1 (Dose Escalation): 100 mg daily. | Drug: CB-03-10<br>* CB-03-10, 100 mg capsule for oral use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose | Determine the maximum tolerated dose (MTD) of CB-03-10 in subjects with advanced solid tumors | 29 days | 
| Determine the dose-limiting toxicity | Determine the dose-limiting toxicity (DLT) of CB-03-10 in subjects with advanced solid tumors | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine a recommended Phase 2 dose (RP2D) of CB-03-10 | Determine a recommended Phase 2 dose (RP2D) of CB-03-10 | 28 days |