A Phase I Study of AK138D1 in the Treatment of Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Solid Cancer
• Interventions: Drug: AK138D1

• Registration Number: NCT06730386
• Lead Sponsor: Akeso

Brief Summary

This is an open-label, first-in-human, Phase I clinical study aimed at evaluating the safety, tolerability, PK, immunogenicity, and preliminary antitumor efficacy of AK138D1 in subjects being treated for advanced solid tumors.

Detailed Description

This study is comprised of two parts: the dose-escalation and dose-expansion stages. Dose-escalation stage aims to determine the MTD/MAD, while the dose-expansion stage is designed to establish the RP2D.

Study Timeline

• Study First Submitted: 2024-12-09
• Study First Submitted QC: 2024-12-09
• Study First Posted: 2024-12-12
• Study Start: 2025-02-24
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-06
• Primary Completion: 2028-02-26
• Study Completion: 2028-08-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. The subject must sign the written informed consent form (ICF) voluntarily;
2. At enrollment, aged ≥ 18 to ≤ 75 years, both males and females are eligible;
3. ECOG performance status score of 0 or 1;
4. Has a life expectancy of ≥ 3 months;
5. Subjects who have histologically or cytologically diagnosed locally advanced or metastatic solid tumor, which Is refractory to or intolerant to standard treatment;
6. At least 1 measurable lesion as per RECIST v1.1 that is suitable for repeated accurate measurement.
7. Adequate organ function.

Exclusion Criteria

1. Prior human epidermal growth factor receptor 3 (HER3) -targeted therapies, including antibodies, antibody-drug conjugates (ADCs), chimeric antigen receptor T-cell immunotherapy (CAR-T), and others;
2. Concomitant participation in another clinical study, unless it is a non-interventional clinical study or the follow-up period of an interventional study;
3. Presence of active central nervous system (CNS) metastases.
4. Patients with a history of non-infectious pneumonitis requiring systemic corticosteroid therapy; a history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis); currently suffering from ILD/pneumonitis or suspected of having such diseases based on imaging during screening;
5. Live vaccines or attenuated live vaccines administered within 4 weeks prior to the first dose, or planned to be administered during the study; use of inactivated vaccines is allowed;
6. Untreated subjects with active hepatitis B (HBsAg positive and HBV-DNA exceeding 1000 copies/mL (200 IU/mL) and above the lower limit of detection). For HBsAg-positive subjects, anti-hepatitis B therapy is required during the study; subjects with active hepatitis C (HCV antibody positive and HCV-RNA levels above the lower limit of detection) is also an exclusion;
7. Known active pulmonary tuberculosis (TB); subjects with suspected active TB must undergo appropriate clinical assessment to rule out the presence of active disease;
8. Active syphilis infection;
9. Subjects with known allergy to any component of any study drug; and with a history of known severe hypersensitivity reactions to other monoclonal antibodies;
10. Other reasons for ineligibility as evaluated by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AK138D1	AK138D1	AK138D1 will be administered in pre-specified dose levels.

Primary Outcome Measures

Name	Time	Method
AEs	Up to approximately 2 years	Incidence and severity of participants with adverse events
Dose-limiting toxicity (DLT)	Up to approximately 2 years	Occurrence of DLTs and determination fo maximum tolerated dose (MTD)

Secondary Outcome Measures

Name	Time	Method
Cmax and Cmin of AK138D1	Up to approximately 2 years	AK138D1 serum drug concentrations in subjects at different time points after administration.
Anti-drug antibodies (ADA)	Up to approximately 2 years	Number of subjects with detectable anti-drug antibodies (ADA).
Objective Response Rate (ORR) assessed by investigator per RECIST v1.1	Up to approximately 2 years	ORR is the proportion of subjects with complete response(CR) or partial response(PR) , assessed by investigators based on RECIST v1.1.
Disease Control Rate (DCR) assessed by investigator per RECIST v1.1	Up to approximately 2 years	Disease control rate (DCR) assessed according to RECIST v1.1.
Duration of response (DoR) assessed by the investigator per RECIST v1.1	Up to approximately 2 years	Duration of response (DoR) assessed according to RECIST v1.1.
Time to response (TTR) assessed by the investigator per RECIST v1.1	Up to approximately 2 years	Time to response (TTR) is defined as the time to response based on RECIST v1.1.
Progression Free Survival (PFS) assessed by investigator per RECIST v1.1	Up to approximately 2 years	PFS is defined as the time from randomization to the first documented disease progression (per RECIST v1.1 criteria) assessed by investigators or death due to any cause, whichever occurs first.
Overall Survival (OS)	Up to approximately 2 years	Overall Survival (OS) is defined as the time from randomization to death due to any cause.

Trial Locations

Locations (4)

Blacktown Hospital-Blacktwon Cancer and Haematology Centre; 🇦🇺 Blacktown, New South Wales, Australia

Macquarie University; 🇦🇺 North Ryde, New South Wales, Australia

ICON Cancer Centre South Brisbane; 🇦🇺 South Brisbane, Queensland, Australia

Peninsula & South Eastern Haematology and Oncology Group; 🇦🇺 Frankston, Victoria, Australia