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

A First-in-human, Phase I Study of Evaluating Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AK138D1 in the Treatment of Advanced Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Cancer
• Intervention / Treatment: Drug: AK138D1

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wenting Li, MD; Phone Number: +86-18116403289; Email: wenting01.li@akesobio.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Not yet recruiting
      • Blacktown Hospital-Blacktwon Cancer and Haematology Centre
      • Principal Investigator: Adnan Nagrial, MD
      • Contact: Adan Nagrial, MD; Phone Number: 0288906859; Email: adnan.nagrial@health.nsw.gov.au
    • North Ryde, New South Wales, Australia, 2109
      • Not yet recruiting
      • Macquarie University
      • Contact: Andrew Parsonson, MD; Phone Number: 0298122956; Email: andrew.parsonson@mqhealth.org.au
      • Principal Investigator: Andrew Parsonson, MD
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Icon Cancer Centre South Brisbane
      • Contact: Jermaine Coward, MD; Phone Number: 0737374500; Email: Jim.Coward@icon.team
      • Principal Investigator: Jermaine Coward, MD
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Recruiting
      • Peninsula & South Eastern Haematology and Oncology Group
      • Principal Investigator: Vinod Ganju, MD
      • Contact: Vinod Ganju, MD; Phone Number: 0397815244; Email: vg@paso.com.au

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK138D1; AK138D1 will be administered in pre-specified dose levels.	Drug: AK138D1; Enrolled subjects will receive intravenous infusion (IV) of AK138D1 according to the dosing regimen specified in their cohort.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Estimated): February 26, 2028
• Study Completion (Estimated): August 30, 2028

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: AK138D1-101

Drug and device information, study documents

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