Study of ASN004 in Patients With Advanced Solid Tumors (ASN004)

An Open Label, Multicenter, Dose-Finding Clinical Phase 1 Study of ASN004 to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy in Patients With Advanced Malignant Solid Tumors

Participants in this study will receive ASN004 once every 3 or 4 weeks by intravenous infusion. The ASN004 dosing schedule may be modified based on emerging data and Safety Review Committee decision. The study will test various doses of ASN004 to find out the highest safe dose to test in future trials.

Eligible subjects will be sequentially enrolled in cohorts at escalated doses.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: ASN004

Detailed Description

Eligible patients will be sequentially enrolled at escalating doses.

Dose escalation decisions will be based on the review of clinical safety and pharmacokinetic (PD) and pharmacodynamics (PD) data and agreed upon by the Sponsor and investigators.

The maximum tolerated dose (MTD) will have an estimated DLT rate of < 33%. Cohorts may be expanded at any dose level or at the MTD for further evaluation of safety, or PK parameters as required.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Texas
    • Austin, Texas, United States, 78758
      • Next Oncology
    • San Antonio, Texas, United States, 78240
      • Next Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Next Oncology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Provide written, voluntary informed consent prior to any -study specific procedure.
2. Histologically confirmed diagnosis of advanced malignant solid tumor.
3. All patients must agree to provide fresh or archival tumor tissue from the tumor lesion that has not been previously irradiated. Patients without archival tissue may only be enrolled if the patient consents to a screening biopsy and this procedure may be safely performed in the judgment of the Investigator.
4. Evidence of progressive disease.
5. For Dose Expansion patients, eligible tumor histologies will be limited to those malignancies known to have highest expression of 5T4 including colorectal, breast, ovarian, lung, liver, and renal carcinomas. A maximum of 3 prior cytotoxic chemotherapy regimens is permitted for advanced disease.
6. Failure of standard therapy or no standard therapy available.
7. Presence of at least 1 measurable target lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 excluding previously irradiated lesions, bone metastasis, or pleural effusion as sole manifestations of disease. Dose escalation patients with evaluable (non-measurable) disease may be permitted to enroll with Medical Monitor approval.
8. Age of at least 18 years old.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
10. A male patient must agree to use contraception as detailed in this protocol during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period.

11. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies.

    i. Not a woman of childbearing potential (WOCBP) OR ii. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of study treatment.

12. Adequate organ function.
13. Patients with Mandatory 5T4 Expression: Patients replacing a previously enrolled non-5T4 expressing patient must consent to and provide fresh or archival tumor tissue to the central pathology laboratory for 5T4 immunohistochemistry (IHC) testing. To be eligible, the patient's tumor must be confirmed by the central pathology laboratory to express 5T4 (H score of ≥ 10).
14. Patient is willing and able to comply with all protocol required visits and assessments.

Exclusion Criteria

1. Hematologic malignancies and lymphomas.
2. Patients with known brain metastases unless the patient has a single lesion or multiple lesions whose sum of the longest diameter is ≤ 1 cm AND who are asymptomatic.
3. Serious concurrent medical conditions.
4. Patients with known history of left ventricular ejection fraction of < 50%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASN004 ascending doses; Patients will receive escalating doses of ASN004 to identify the best dose for further study.	Drug: ASN004; ASN004 is an antibody-drug conjugate for the treatment of advanced or metastatic solid tumors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the maximum tolerated dose of ASN004	The MTD will be determined by evaluating the number of subjects with treatment related adverse events (AEs) and DLTs.	first 21 days for patients administered ASN004 every 3 weeks, and first 28 days for patients administered ASN004 every 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculate the pharmacokinetic (PK) area under the plasma concentration of ASN004	Calculate the amount of ASN004 in the bloodstream	First 63 days
Calculate the maximum plasma concentration at steady state	Calculate the maximum amount of ASN004 in the bloodstream	First 63 days
Calculate the terminal elimination rate of ASN004	Calculate how fast ASN004 leaves the body	First 63 days
Change in the size of measurable tumor lesions	Change from baseline in the sum of the longest dimension in millimeters or each measurable lesion	up to 1 year
Change in the status of non-measurable tumor lesions	Number of subjects that have resolution on non-measurable tumor lesions	Up to 1 year
Appearance of new tumor lesions	Number of subjects with new lesions	Up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlate 5T4 oncofetal protein (5T4) expression and clinical efficacy	Number of patients with 5T4 expression that have a complete response, partial response or prolonged stable disease when receiving ASN004.	Up to 1 year

Collaborators and Investigators

• Sponsor: Kirilys Therapeutics Inc.
• Investigators: Study Director: Alison L Hannah, MD, Kirilys Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2022
• Primary Completion (Actual): May 8, 2024
• Study Completion (Actual): May 8, 2024

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: antibody-drug conjugate; immunoconjugate; General Solid Tumors
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms
• Other Study ID Numbers: ASN004-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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