A Study of AK146D1 for Injection in the Treatment of Advanced Solid Tumors

A Phase Ia Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of AK146D1 for Injection, an Anti-Trop2/Nectin4 Bispecific Antibody-drug Conjugate, in Patients With Advanced Solid Tumors

This is an first-in-human, Phase I clinical study aimed at evaluating the safety, tolerability, PK, immunogenicity, and preliminary antitumor efficacy of AK146D1 for injection in advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: AK146D1 for injection

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ting Liu; Phone Number: +86(0760)8987 3999; Email: clinicaltrials@akesobio.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia
      • Recruiting
      • Scientia Clinical Research
      • Contact: Christina Teng; Phone Number: 61 2 9382 5806; Email: Christina.Teng@scientiaclinicalresearch.com.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be able to understand and voluntarily sign the written informed consent form.
2. Aged of ≥ 18 years and ≤75 years.
3. ECOG PS 0 or 1.
4. The expected lifespan is ≥3 months.
5. Histologically-confirmed unresectable advanced solid tumors with disease progression or intolerance to standard treatment or no standard treatment available.
6. At least one measurable lesion according to RECIST v1.1.
7. Have sufficient organ function.
8. Females subjects must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception

Exclusion Criteria:

1. Having other active malignancies within 3 years.
2. Currently participating in another interventional clinical study.
3. Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
4. Having received any treatment targeting Trop2 or Nectin4 or any treatment with topoisomerase I inhibitor agents.
5. Having received systemic anti-tumor treatment within 4 weeks or 1 cycle interval of the regimen or major surgical operations within 4 weeks before the first administration.
6. Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 5.0 grade 1 or lower.
7. Subjects with clinically significant cardiovascular or cerebrovascular diseases or risks.
8. Subjects with active autoimmune diseases requiring systemic treatment within 2 years.
9. Known active infection requiring antibodies treatment within 2 weeks, or severe infection within 4 weeks prior to the first dose.
10. Known to be positive for HIV and other infections.
11. Previous history of severe hypersensitivity reactions.
12. Live attenuated vaccines were received within 4 weeks.
13. Subjects with a history of mental illness and incapacitated or limited capacity.
14. Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.

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: AK146D1 for injection; AK146D1 for injection will be administered in pre-specified dose levels	Drug: AK146D1 for injection; AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with dose limiting toxicities (DLTs)	DLTs are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug.	During the first 3 weeks of treatment.
Number of participants with adverse events (AEs)	AEs refer to any untoward medical occurrence or deterioration of existing medical events after the participants sign the ICFs, whether or not considered related to the study treatment.	From the time of informed consent signed through 90 days after the last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-drug antibodies (ADA)	The number and percentage of participants with detectable anti-drug antibodies (ADA)	From pre-dose to 90 days post end of treatment
Objective Response Rate (ORR) assessed by investigator per RECIST v1.1	ORR is the proportion of participants with complete response(CR) or partial response(PR) , assessed based on RECIST v1.1.	Up to approximately 2 years
Disease Control Rate (DCR) assessed per RECIST v1.1	DCR is defined as the proportion of participants with CR, PR, or SD, assessed based on RECIST v1.1.	Up to approximately 2 years
Duration of response (DoR) assessed by the investigator per RECIST v1.1	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first.	Up to approximately 2 years
Time to response (TTR) assessed by the investigator per RECIST v1.1	TTR is defined as the time to objective response based on RECIST v1.1.	Up to approximately 2 years
Progression Free Survival (PFS) assessed by investigator per RECIST v1.1	PFS is defined as the time from the start of treatment until the first documentation of disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first.	Up to approximately 2 years
Overall survival (OS)	OS is defined as the time from the first dose to death from any cause.	Up to approximately 2 years
Serum PK concentration of AK146D1	Serum PK concentration of AK146D1 in participants after administration	From pre-dose to the end of the last dose, an average of 6 months.

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Hui Gan, Austin Health

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2025
• Primary Completion (Estimated): November 5, 2026
• Study Completion (Estimated): May 5, 2027

Study Registration Dates

• First Submitted: March 16, 2025
• First Submitted That Met QC Criteria: April 8, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 14, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AK146D1-102

Drug and device information, study documents

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