A Study of CLN-619 Alone and in Combination With Pembrolizumab in Advanced Solid Tumors

• Drug: CLN-619
• Drug: Pembrolizumab

Inclusion Criteria:

1. Males or females aged ≥ 18 years.
2. Willing and able to give written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. and adhere to protocol requirements; written informed consent and any locally required authorization must be obtained from the patient prior to performing any protocol-related procedures, including screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening evaluations.
3. Module A Monotherapy Dosethe amount of medication taken Escalation Cohort and Module B Combination Therapy Dose Escalation Cohorts: Histologically or cytologically-confirmed metastatic or locally advanced, unresectable solid tumors. For Module B, tumor type is listed as an approved indication per the current prescribing information for pembrolizumab.
4. Module A Cohort Expansions:
   1. Expansion A1: Histologically or cytologically-confirmed metastatic or locally advanced, unresectable NSCLC;
   2. Expansion A2: Histologically or cytologically-confirmed metastatic or locally advanced, unresectable cervical cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs.
   3. Expansion A3 and A4: Histologically or cytologically-confirmed metastatic or locally advanced, unresectable endometrial cancer.
   4. Eligibility for disease-specific expansion cohorts may be further refined by histologic subtype, molecular features, or exposure to prior therapy based on clinical, pharmacodynamic, or biomarker data emerging from the study.
5. Module B Cohort Expansions:
   1. Expansion B1: Histologically or cytologically-confirmed metastatic or locally-advanced, unresectable NSCLC.
   2. Expansion B2: Histologically or cytologically-confirmed metastatic or locally-advanced, unresectable endometrial.
   3. Eligibility for disease-specific expansion cohorts may be further refined by histologic subtype, molecular features, or exposure to prior therapy based on clinical, pharmacodynamic, or biomarker data emerging from the study.
6. Prior treatment history as follows:a) Patients should have received any other approved standard therapy that is available to the patient, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient. In the case of a patient declining such therapy, documentation that the patient has been informed and declined should be documented in the medical record.
7. Baseline measurable disease based on RECIST v1.1 for Module A escalation, Module B escalation; and, both Module A and Module B expansion cohorts. Patients are required to have one or more measurable lesions that meet RECIST v1.1 and meet the following conditions:
   1. A non-lymph nodea small lump or mass of tissue in your body lesion that has a longest unidimensional measurement of ≥ 10 mm or a lymph node lesion that has a shortest unidimensional measurement of ≥ 15 mm;
   2. 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 prior to enrollment, and the longest unidimensional measurement is ≥ 10 mm.
8. Performance status of 0 or 1 based on the Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance scale.
9. Estimated life expectancy of 12 weeks or greater.
10. Prior palliative radiotherapy must have been completed 14 days prior to dosing on C1D1.
11. Toxicities related to prior study therapy should have resolved to Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 1 or less according to criteria of NCI CTCAE v5.0, except for alopeciathe partial or complete absence of hair from areas of the body where it normally grows; baldness. Peripheral neuropathy should be clinically stable or improving and be Grade 2 or less in severity. Patients with chronica long-lasting disease that changes slowly over time but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
12. Have adequate liver and kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body function and hematological parameters within a normal range as defined by:
    1. 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;
    2. AST and ALT ≤ 2.5x ULN or ≤ 5x ULN for patients with liver metastases;
    3. Creatinine clearance (CrCl) ≥ 45 mL/min as measured or estimated using Cockcroft-Gault formula;
    4. Hemoglobin ≥ 8 g/dL without bloodthe red bodily fluid that transports oxygen and other nutrients around the body transfusions for at least two weeks prior to dosing on C1D1;
    5. Absolute neutrophil count ≥ 1500 cellsthe basic structural and functional unit of all living things/mm3 without growth factor support, three days for filgrastim, 14 days for pegfilgrastim;
    6. Platelet count ≥ 75,000 cells/mm3.
13. Patients in the Module A and Module B dose escalation cohorts must have archival tissuea group of cells that work together to perform a function for biomarker analysis. A fresh biopsyremoval of a section of tissue to analyse for cancer cells is required if archival tissue is unavailable.