AK146D1 injection for advanced solid tumors.

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

This will test whether AK146D1 injection is safe and shows early anti-tumor activity in adults with advanced solid tumors who have progressed on or cannot receive standard treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Akeso (industry)
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07067567 on ClinicalTrials.gov

What this trial studies

This first-in-human Phase I trial gives AK146D1 by injection to adults with unresectable or metastatic solid tumors. The study's primary goals are to characterize safety, tolerability, pharmacokinetics, and immunogenicity, with secondary evaluation of preliminary antitumor activity. Eligible participants must have measurable disease per RECIST v1.1, ECOG performance status 0–1, adequate organ function, and be aged 18–75, while those with recent other active malignancies, active untreated CNS metastases, or prior therapies targeting Trop2 or Nectin4 are excluded. The study is conducted at Sun Yat-sen University Cancer Center in Guangzhou and will follow a dose-escalation first-in-human design.

Who should consider this trial

Good fit: Adults 18–75 with histologically confirmed unresectable advanced solid tumors that have progressed after or are unsuitable for standard therapy, with ECOG 0–1, measurable disease, and adequate organ function are ideal candidates.

Not a fit: Patients with active untreated CNS metastases, other recent active malignancies, prior Trop2 or Nectin4-targeted therapy, poor organ function, or ECOG >1 are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, AK146D1 could become a new treatment option that slows tumor growth or shrinks tumors in patients with advanced solid cancers who have few other options.

How similar studies have performed: Other therapies targeting Trop2 (for example sacituzumab govitecan) and Nectin4 (for example enfortumab vedotin) have shown clinical activity in some cancers, but AK146D1 itself is novel and unproven in humans.

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.
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.

Where this trial is running

Guangzhou, Guangdong

• SunYat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Ting Liu

Conditions: Advanced Solid Tumors