Clinical trial NCT06929663: A Study of AK146D1 for Injection in the Treatment of Advanced Solid Tumors
Official title: A Phase Ia Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of AK146D1 for Injection, an Anti-Trop2/Nectin4 Bispecific Antibody-drug Conjugate, in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2025-04-16
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an first-in-human, Phase I clinical study aimed at evaluating the safety, tolerability, PK, immunogenicity, and preliminary antitumor efficacy of AK146D1 for injection in advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

1. Be able to understand and voluntarily sign the written informed consent form.
2. Aged of ≥ 18 years and ≤75 years.
3. ECOG PS 0 or 1.
4. The expected lifespan is ≥3 months.
5. Histologically-confirmed unresectable advanced solid tumors with disease progression or intolerance to standard treatment or no standard treatment available.
6. At least one measurable lesion according to RECIST v1.1.
7. Have sufficient organ function.
8. Females subjects must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception

Exclusion Criteria:

1. Having other active malignancies within 3 years.
2. Currently participating in another interventional clinical study.
3. Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
4. Having received any treatment targeting Trop2 or Nectin4 or any treatment with topoisomerase I inhibitor agents.
5. Having received systemic anti-tumor treatment within 4 weeks or 1 cycle interval of the regimen or major surgical operations within 4 weeks before the first administration.
6. Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 5.0 grade 1 or lower.
7. Subjects with clinically significant cardiovascular or cerebrovascular diseases or risks.
8. Subjects with active autoimmune diseases requiring systemic treatment within 2 years.
9. Known active infection requiring antibodies treatment within 2 weeks, or severe infection within 4 weeks prior to the first dose.
10. Known to be positive for HIV and other infections.
11. Previous history of severe hypersensitivity reactions.
12. Live attenuated vaccines were received within 4 weeks.
13. Subjects with a history of mental illness and incapacitated or limited capacity.
14. Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.

Primary outcomes:
measure: Number of participants with dose limiting toxicities (DLTs)
timeFrame: During the first 3 weeks of treatment.
measure: Number of participants with adverse events (AEs)
timeFrame: From the time of informed consent signed through 90 days after the last dose of study drug
Secondary outcomes:
measure: Serum PK concentration of AK146D1
timeFrame: From pre-dose to 14 days after the first dose on Cycle 1
measure: Anti-drug antibodies (ADA)
timeFrame: From pre-dose to 90 days post end of treatment
measure: Objective Response Rate (ORR) assessed by investigator per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Disease Control Rate (DCR) assessed 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:
Study officials:
affiliation: Austin Health
name: Hui Gan
role: PRINCIPAL_INVESTIGATOR
References: