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.

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.

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.