A Phase 1 First-in-Human Study to Investigate the Safety, Efficacy, PK, and Pharmacodynamic Activity of CLN-617 Alone and in Combination with Pembrolizumab in Patients with Advanced Solid Tumors
A Phase 1 First-In-Human Study to Investigate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamic Activity of CLN-617 Alone and in Combination with Pembrolizumab in Patients with Advanced Solid Tumors
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Clinical Trial Information
Trial Contact: Bobe Cortes, Estefania; Casillas, Bridey L; Simoni, Christine
Trial Phone: 321.841.6626 ; 321.841.8284 ; 321.841.7293
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IRB No: WIRB20232365
Protocol Abbrev: CLN-617-001
Principal Investigator: Sajeve Samuel Thomas, MD
Phase: Drug: Phase I
Age Group: Adult
Secondary Protocol No: CLN-617-001
Treatment: CLN-617 administered intratumorally alone or in combination with pembrolizumab
Therapies Involved: Medication
ClinicalTrials.gov ID: NCT06035744
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Objective
To characterize the safety, tolerability, dose limiting toxicities (DLT), of CLN-617 administered intratumorally alone or in combination with pembrolizumab in patients with advanced solid tumors.
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Key Eligibility
Inclusion Criteria
No exceptions will be granted by the Sponsor.
1. Aged ≥ 18 years.
2. Willing and able to give written informed consent and adhere to protocol requirements. written informed consent and any locally required authorization must be obtained from the patient prior to performing any protocol-specific procedures.
3. Patients should have previously received or had a contraindication to standard therapy that confers an overall survival benefit.
4. Part 1 Dose Escalation Cohorts: Histologically or cytologically confirmed advanced incurable or metastatic non-neurological solid tumor with accessible injectable lesions.
5. Part 2 Dose Optimization: Histologically or cytologically confirmed select advanced incurable or metastatic cancer types with accessible injectable lesions.
6. Part 3 Dose Expansions:
a) Cohort 1: Histologically or cytologically confirmed metastatic or locally advanced, unresectable melanoma with accessible injectable lesions.
b) Cohort 2: Histologically or cytologically confirmed metastatic or locally advanced, unresectable HNSCC with accessible injectable lesions.
7. Patients must have 2 or more measurable lesions for Part 1, or one or more measurable lesions for Part 2 and Part 3 that meet RECIST v1.1. Also, patients must have tumors able to be palpable, visualized on ultrasound without encasing with blood vessels, amenable to direct injection, and meet one of the following conditions:
a) A non-lymph node lesion, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm.
b) A lymph node lesion that has the shortest unidimensional measurement of ≥ 15 mm.
c) Lesions that have received previous local treatment, such as radiotherapy or ablation, can also be used as measurable target lesions if progression has been confirmed according to RECIST v1.1 before enrollment, and the longest unidimensional measurement is ≥ 10 mm for non-lymph node lesions and > 15 mm for lymph nodes.
8. Patients deemed appropriate for pembrolizumab treatment based on the tumor type and prior available therapy, per the judgment of the investigator.
9. Performance status of 0 or 1 based on the Eastern Cooperative Oncology Group (ECOG) performance scale.
10. Estimated life expectancy at least 12 weeks or longer.
11. Toxicities related to prior study therapy should have resolved to Grade 1 or less according to criteria of NCI CTCAE v5.0, except for alopecia. Patients with chronic but stable Grade 2 toxicities may be allowed to enroll after an agreement between the Investigator and Sponsor.
12. Have adequate liver and kidney function and hematological parameters within a normal range as defined by:
a) Total bilirubin ≤ 1.5x ULN. This does not apply for patients with confirmed Gilbert’s Syndrome, for whom total bilirubin must be less than 3.0 mg/dL with a conjugated bilirubin less than 0.5 mg/dL.
b) AST and ALT ≤ 2.5x ULN or ≤ 5x ULN for patients with liver metastases.
c) Estimated creatinine clearance (CrCL) ≥ 50 mL/min by using Cockcroft-Gault formula.
d) Hemoglobin ≥ 8 g/dL without blood transfusions for at least two weeks prior to dosing on C1D1.
e) Absolute neutrophil count ≥ 1500 cells/mm3 without growth factor support (e.g., three days for filgrastim, 14 days for pegfilgrastim).
f) Platelet count ≥ 100,000 cells/mm3.
13. Patients in dose escalation
(Part 1) must agree to provide a fresh biopsy at baseline, and on-treatment biopsies from both injected and uninjected tumors, at the end of Cycle 1 (mandatory) and at the end of Cycle 3 (strongly encouraged).
14. Patients in dose optimization
(Part 2) and dose-expansion
(Part 3) must agree to provide a fresh biopsy at baseline, and an on-treatment biopsy from both injected and uninjected tumors at the end of Cycle 2. If a biopsy cannot be performed with acceptable clinical risk in the judgment of the Investigator, the Sponsor’s medical monitor must be contacted to approve enrollment.
