Clinical trial NCT06730386: A Phase I Study of AK138D1 in the Treatment of Advanced Solid Tumors
Official title: A First-in-human, Phase I Study of Evaluating Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AK138D1 in the Treatment of Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Cancer
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2024-12-12
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: AEs
timeFrame: Up to approximately 2 years
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Cmax and Cmin of AK138D1
timeFrame: Up to approximately 2 years
measure: Anti-drug antibodies (ADA)
timeFrame: Up to approximately 2 years
measure: Objective Response Rate (ORR) assessed by investigator per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Disease Control Rate (DCR) assessed by investigator per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Duration of response (DoR) assessed by the investigator per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Time to response (TTR) assessed by the investigator per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Progression Free Survival (PFS) assessed by investigator per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Blacktown
country: Australia
facility: Blacktown Hospital-Blacktwon Cancer and Haematology Centre
state: New South Wales
city: North Ryde
country: Australia
facility: Macquarie University
state: New South Wales
city: South Brisbane
country: Australia
facility: ICON Cancer Centre South Brisbane
state: Queensland
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
Study officials:
References: