CLN-418 Study on Subjects With Advanced Solid Tumors

Study Overview
=================
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.

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

Conditions
-----------------
Advanced Solid Tumor

Intervention / Treatment
-----------------
* Drug: CLN-418


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willingness to sign a written informed consent document. Male or female subject aged ≥18 years old at the time of screening. 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. Adequate organ and bone marrow function. Exclusion Criteria: Prior used anti-B7H4 and/or anti-4-1BB antibody treatment. 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. Not yet recovered from surgery or (immune-related) toxicity related with previous treatment. Known history or active infection of hepatitis B or C. History of cirrhosis or non-alcohol steatohepatitis, alcohol or drug-related, autoimmune hepatitis. Known brain metastases or other central nervous system metastases that are either symptomatic or untreated that require concurrent treatment. Active infection that requires treatment with antibiotics or antiviral treatment within 3 weeks prior to first dose of investigational product. Known history of infection with human immunodeficiency virus or known acquired immunodeficiency syndrome (AIDS). Known autoimmune disease. Clinically significant cardiac condition. Pregnant or breastfeeding women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation (Part 1) followed by Dose expansion (Part 2)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CLN-418: Part 1<br>Experimental Part 1: Dose escalation Intravenous IV administrations of CLN-418 on Day 1 of each 21 day treatment cycle Dose for cohorts to be confirmed following consultation and approval by Safety Review Committee | Drug: CLN-418<br>* Intravenous (IV) administration<br>* Other names: HBM7008;|
| Experimental: CLN-418: Part 2<br>Experimental Part 2: Dose Expansion Treatment administered at Maximum Tolerated Dose (MTD) and / or Recommended Phase 2 Dose (RP2D) established in Part 1 | Drug: CLN-418<br>* Intravenous (IV) administration<br>* Other names: HBM7008;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with dose-limiting toxicity (DLT) | Number of subjects who experienced DLT events during 21 days after first administration of CLN-418, divided by the number of DLT evaluable Subjects | From Day 1 until day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | Number of participants with Adverse Events (including vital signs, physical examinations, and abnormal laboratory parameters). | From signing of Informed Consent Form (ICF) till 84 days after last dose | 
| 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 | 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 | 
| Duration of response | 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. | 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 | 
| Disease control rate | The proportion of subjects with a best overall response of Complete Response (CR), Partial Response (PR), or stable disease (SD). | 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. | 
| Duration of disease control | 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 | 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. | 
| Maximal tumor shrinkage | The greatest tumor shrinkage achieved at any follow-up assessment | 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 | 
| Pharmacokinetics Analysis - Serum Concentration | Reporting of serum concentration of CLN-418 | Up to 84 days post last dose | 
| Anti-drug antibodies | Measure of detectable Anti-drug antibody (ADA) and neutralizing antibodies in serum samples at specific study timepoints | Up to 84 days post last dose | 
| Pharmacokinetics Analysis - Time Deviation | Reporting time deviation data of CLN-418 | Up to 84 days post last dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced Solid Tumors