Advanced Solid Tumor
Conditions
Keywords
Advanced Solid Tumors
Brief summary
Study to evaluate the safety and tolerability of the study drug CLN-418, to determine the maximum tolerated dose and/or recommended Phase 2 study dose of CLN-418.
Detailed description
This is a study to evaluate the safety and tolerability of the study drug CLN-418, and to determine the maximum tolerated dose and/or recommended Phase 2 study dose of CLN-418. The study will also look at the anti-tumor activity, pharmacokinetics and immunogenicity of CLN-418.The study consists of 2 parts. In Part 1, patients are enrolled into different cohort doses in order to identify the appropriate recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD). In Part 2, participants with metastatic / unresectable Non small cell lung cancer (NSCLC), Triple Negative Breast Cancer (TNBC) will receive the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) established in Part 1 of the study. In Part 1 and Part 2, participants will be administered treatment every 3 weeks.
Interventions
DRUGCLN-418
Intravenous (IV) administration
Sponsors
Harbour BioMed US, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation (Part 1) followed by Dose expansion (Part 2)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willingness to sign a written informed consent document. 2. Male or female subject aged ≥18 years old at the time of screening. 3. Histologically or cytologically confirmed advanced solid tumors (e.g., breast cancer, ovarian cancer, endometrial cancer, cervical cancer, squamous cell non-small cell lung cancer (sNSCLC), cholangiocarcinoma, esophagus cancer, urothelial carcinoma, head and neck squamous cell carcinoma (HNSCC)), followed by dose-expansion cohorts (Part 2) of subjects with advanced and/or metastatic non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC).or recurrent and progressed since last antitumor therapy for which no alternative, curative standard therapy exists. 4. Adequate organ and bone marrow function.
Exclusion criteria
1. Prior used anti-B7H4 and/or anti-4-1BB antibody treatment. 2. Immuno-oncology therapy or targeted anti-cancer therapy within 4 weeks prior to first dose of investigational product, any other anti-cancer therapy within 2 weeks prior to first dose of investigational product. 3. Not yet recovered from surgery or (immune-related) toxicity related with previous treatment. 4. Known history or active infection of hepatitis B or C. 5. History of cirrhosis or non-alcohol steatohepatitis, alcohol or drug-related, autoimmune hepatitis. 6. Known brain metastases or other central nervous system metastases that are either symptomatic or untreated that require concurrent treatment. 7. Active infection that requires treatment with antibiotics or antiviral treatment within 3 weeks prior to first dose of investigational product. 8. Known history of infection with human immunodeficiency virus or known acquired immunodeficiency syndrome (AIDS). 9. Known autoimmune disease. 10. Clinically significant cardiac condition. 11. Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with dose-limiting toxicity (DLT) | From Day 1 until day 21 | Number of subjects who experienced DLT events during 21 days after first administration of CLN-418, divided by the number of DLT evaluable Subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Analysis - Time Deviation | Up to 84 days post last dose | Reporting time deviation data of CLN-418 |
| Adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | From signing of Informed Consent Form (ICF) till 84 days after last dose | Number of participants with Adverse Events (including vital signs, physical examinations, and abnormal laboratory parameters). |
| Objective response rate, defined as the proportion of subjects with best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 | From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months | Proportion of subjects with best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 |
| Duration of response | From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months | The time interval from first occurrence of a documented objective response to the time of disease progression as determined by the Investigator using RECIST 1.1 or death from any cause, whichever comes first. |
| Anti-drug antibodies | Up to 84 days post last dose | Measure of detectable Anti-drug antibody (ADA) and neutralizing antibodies in serum samples at specific study timepoints |
| Duration of disease control | From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months. | The time from the date of start of treatment to the date of disease progression or death for subjects who had CR or PR or SD during treatment |
| Maximal tumor shrinkage | From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months | The greatest tumor shrinkage achieved at any follow-up assessment |
| Pharmacokinetics Analysis - Serum Concentration | Up to 84 days post last dose | Reporting of serum concentration of CLN-418 |
| Disease control rate | From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months. | The proportion of subjects with a best overall response of Complete Response (CR), Partial Response (PR), or stable disease (SD). |
Countries
Australia, United States
Outcome results
None listed