Overview

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.

Eligibility

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.