A Phase II Study of AK146D1 Mono or Combined With AK112 in Advanced Urothelial Carcinoma

A Phase II Clinical Study to Evaluate the Safety，Tolerability，Pharmacokinetics and Anti-tumor Efficacy of AK146D1 Monotherapy or Combined With AK112 in Patients With Advanced Urothelial Carcinoma

This is a Phase II clinical study aimed at evaluating the safety, tolerability, antitumor efficacy, PK and immunogenicity of AK146D1 monotherapy or combined with AK112 in advanced Urothelial carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Urothelial Carcinoma (UC)
• Intervention / Treatment: Drug: AK146D1 for injection; Drug: AK112 Injection

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
    • Contact: Dingwei Ye; Phone Number: 021-64175590; Email: dwyeli@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Be able to understand and voluntarily sign the written informed consent form.
• Age 18-75.
• ECOG PS 0 or 1.
• Expected lifespan ≥3 months.
• Histologically or cytologically documented Urothelial carcinoma.
• At least one measurable lesion according to RECIST v1.1.
• Sufficient organ function.

Exclusion Criteria:

• Having other active malignancies within 3 years.
• Currently participating in another interventional clinical study.
• Presence of active metastases to the central nervous system.
• Prior chemotherapy agent targeting topoisomerase I .
• Receipt of systemic anti-tumor therapy within 4 weeks prior to the first dose.
• Patients with clinically significant cardiovascular or cerebrovascular diseases or risks.
• Patients with active autoimmune diseases requiring systemic treatment within 2 years.
• Receipt of systemic anti-infective therapy within 2 weeks prior to the first dose.
• Previous history of severe hypersensitivity reactions.
• Patients with a history of mental illness and incapacitated or limited capacity.
• Any disease or condition that, in the opinion of the investigator, would compromise patient safety or interfere with study assessments.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; AK146D1 combined with AK112	Drug: AK146D1 for injection; AK146D1 for injection is an antiTrop2/Nectin4 bispecific antibody-drug conjugate; Drug: AK112 Injection; AK112 Injection is a PD-1/VEGF bispecific antibody
Experimental: Arm B; AK146D1 mono	Drug: AK146D1 for injection; AK146D1 for injection is an antiTrop2/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 predefined severity criteria, and assessed as having a suspected relationship to study drug	During the first 3 weeks of treatment
Objective Response Rate(ORR)	ORR is the proportion of participants with complete response(CR) or partial response(PR)	Up to 2 years
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival(PFS)	PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause,whichever occurs first.	Up to 2 years
Disease Control Rate(DCR)	DCR is defined as the proportion of participants with CR, PR, or SD	Up to 2 years
Duration of response(DoR)	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.	Up to 2 years
Time to response(TTR)	TTR is defined as the time to objective response	Up to 2 years
Overall survival(OS)	OS is defined as the time from the first dose to death from any cause.	Up to 2 years

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Estimated): June 22, 2026
• Primary Completion (Estimated): August 24, 2028
• Study Completion (Estimated): August 24, 2028

Study Registration Dates

• First Submitted: June 4, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Therapeutics; Drug Administration Routes; Drug Therapy; Injections
• Other Study ID Numbers: AK146D1-203

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