CLN-418 Study on Subjects With Advanced Solid Tumors

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 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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Meagan Sardinha; Phone Number: +1-617-410-4650; Email: ClinOps@cullinanoncology.com

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Recruiting
      • St George private Hospital
      • Contact: Tracy Liaw; Email: liawt@ramsayhealth.com.au
      • Principal Investigator: Kate Wilkinson, MBBS FRACP
    • Wollongong, New South Wales, Australia, 2500
      • Recruiting
      • Southern Medical Day Care Centre
      • Principal Investigator: Philip Clingan
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center
      • Principal Investigator: Anthony El-Khoureiy, MD
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
      • Principal Investigator: Manish Patel, MD
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Recruiting
      • Carolina BioOncology Institute - Cancer Research Centre
      • Principal Investigator: John D Powderly II, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson
      • Principal Investigator: Sarina Piha-Paul, MD
    • Irving, Texas, United States, 75039
      • Recruiting
      • NEXT Oncology
      • Principal Investigator: Shiraj Sen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLN-418: Part 1; 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; Intravenous (IV) administration; Other Names: HBM7008
Experimental: CLN-418: Part 2; 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; Intravenous (IV) administration; 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
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
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
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
Pharmacokinetics Analysis - Serum Concentration	Reporting of serum concentration of CLN-418	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

Collaborators and Investigators

• Sponsor: Cullinan Oncology Inc.
• Collaborators: Harbour BioMed US, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CLN-418-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data generated by this study will be considered confidential by the Investigator, except to the extent that it is included in a publication. The general strategy regarding publication of the study will be mutually agreed upon by the Investigator and Sponsor. The Sponsor reserves the right to manage the publication of all study results. The Investigator agrees that oral and written communication to third parties of any procedures or results from the study is subject to prior written consent of the Sponsor. Presentation material and/or manuscript(s) for publication will be reviewed by the Sponsor prior to submission for publication. Alterations in the material will only be made in agreement between the Investigator and the Sponsor

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No