Clinical trial NCT05306444: CLN-418 Study on Subjects With Advanced Solid Tumors
Official title: A Phase 1 Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of CLN-418 in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: Advanced Solid Tumors
Lead sponsor: Harbour BioMed US, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-01
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation (Part 1) followed by Dose expansion (Part 2)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of subjects with dose-limiting toxicity (DLT)
timeFrame: From Day 1 until day 21
Secondary outcomes:
measure: Adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
timeFrame: From signing of Informed Consent Form (ICF) till 84 days after last dose
measure: 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
timeFrame: 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
measure: Duration of response
timeFrame: 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
measure: Disease control rate
timeFrame: 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.
measure: Duration of disease control
timeFrame: 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.
measure: Maximal tumor shrinkage
timeFrame: 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
measure: Pharmacokinetics Analysis - Serum Concentration
timeFrame: Up to 84 days post last dose
measure: Anti-drug antibodies
timeFrame: Up to 84 days post last dose
measure: Pharmacokinetics Analysis - Time Deviation
timeFrame: Up to 84 days post last dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Huntersville
country: United States
facility: Carolina BioOncology Institute - Cancer Research Centre
state: North Carolina
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Irving
country: United States
facility: NEXT Oncology
state: Texas
city: Kogarah
country: Australia
facility: St George Private Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
Study officials:
References: