Locally Advanced / Metastatic Solid Tumors
Conditions
Keywords
solid tumors, metastatic, VEGF, PD-1, anti-PD-1, anti VEGF, immuno-oncology, anti-angiogenic therapy, checkpoint inhibitor, metastatic cancer, advanced cancer, First-in-Human, Dose Escalation, Dose Optimization
Brief summary
The purpose of this study is to determine the safety and tolerability of monotherapy CR-001 and identify the maximum tolerated dose (MTD), and/or optimal biologic dose and Recommended Phase 2 Dose(s) (RP2D) in participants with locally advanced or metastatic solid tumors.
Detailed description
The study will initially comprise 3 parts: dose escalation, backfill, and dose optimization cohorts. The study will follow a stepwise approach, beginning with a typical dose escalation in participants with selected indications of advanced solid tumors. Additional participants will enroll in the backfill part at select dose levels that have been previously cleared for safety by the safety review committee. In dose optimization, participants will be randomized to one of two CR-001 dose levels. All participants will undergo a screening period, a treatment period of up to 2 years, a safety follow-up period, and long-term efficacy and survival follow-up. During the treatment period, participants will undergo clinical and safety assessments including disease assessment scans and blood laboratory safety, pharmacokinetic, and pharmacodynamic assessments. After treatment ends, disease scans will continue until disease progression, and long-term follow-up visits will be conducted by telephone every 3 months.
Interventions
DRUGCR-001
Intravenous Infusion
Sponsors
Crescent Biopharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Life expectancy ≥ 3 months * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 - 1 * Adequate organ function and hematologic reserve based on laboratory parameters * Have measurable disease defined by RECIST v1.1 * For Backfill and Dose Optimization: Willingness to provide recent archival tumor tissue sample or willingness to undergo biopsy * Tumor Indication specific inclusion criteria: * For dose escalation or backfill: progressing from, intolerant to, or ineligible for (due to unavailability or contraindication) local standard of care therapies and have one of the following locally advanced or metastatic tumor types: * Hepatocellular carcinoma * Biliary tract cancer * Endometrial carcinoma * Cervical cancer * Ovarian cancer * Gastric or gastroesophageal cancer * Colorectal cancer * Non-small cell lung cancer Key
Exclusion criteria
* Has malignancies other than disease under study within the past 3 years * Has conditions requiring treatment with clinically significant or increasing doses of systemic steroid therapy * Has not adequately recovered from recent major surgery * Has ongoing clinically significant toxicity related to prior therapy * Has active central nervous system (CNS) metastases * Has active autoimmune disease requiring systemic therapy in the past 2 years (replacement therapy is permitted) * Has a history of serious Grade ≥ 3 immune-related adverse event (irAE) * Has a history of noninfectious pneumonitis/interstitial lung disease * Has an active severe infection * Has received a live or attenuated vaccine within 30 days of the first dose * Has undergone prior allogeneic stem cell or solid organ transplantation * Has protocol-specified events related to gastrointestinal perforation, surgery, wound healing complications, and bleeding * Has clinically significant cardiovascular disease NOTE: Other protocol defined Inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation - Incidence and nature of dose-limiting toxicities | From the first dose of study drug up until approximately 1 month | Per cohort |
| Dose Escalation - Characterization of the maximum tolerated dose, if applicable | From the first dose of study drug up until approximately 1 month | Per Cohort |
| All parts - Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and treatment - emergent serious adverse events | From the first dose of study drug until 90 days after the last dose of study drug | Events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) |
| All parts - Incidence and severity of TEAEs leading to dose modifications | From the first dose of study drug until 90 days after the last dose of study drug | — |
| All parts - Incidence and severity of TEAEs leading to treatment discontinuation | From the first dose of study drug until 90 days after the last dose of study drug | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All parts - Determination of recommended Phase 2 dose(s) | From the first dose of study drug until 90 days after the last dose of study drug | — |
| All parts - Serum CR-001 pharmacokinetic parameters | Predose until up to approximately 36 months | AUC0--inf after a single dose and steady state parameters, as appropriate |
| All parts - Incidence of participants with detectable antidrug antibodies | Predose until up to approximately 36 months | — |
| All parts - Overall response rate | From the first dose of study drug until up to approximately 36 months | — |
| All parts - Duration of response | From the first dose of study drug until up to approximately 36 months | — |
| All parts - Time to response | From the first dose of study drug until up to approximately 36 months | — |
| All parts - Progression free survival | From the first dose of study drug until up to approximately 36 months | — |
| All parts - Overall survival | From the first dose of study drug until up to approximately 36 months | — |
| All parts - Best percent change in target lesions | From the first dose of study drug until up to approximately 36 months | — |
Countries
Australia, Ireland, Italy, Romania, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTCrescent Clinical Trials
STUDY_DIRECTORBrad Sumrow, MD
Crescent Biopharma, Inc.
Outcome results
None listed