A Phase II Study of AK146D1 in Combination With AK112 in Advanced Non-Small Cell Lung Cancer

NCT07669779 | Recruiting Phase 2

• 1 other identifier: AK146D1-201
• Study Type: interventional
• Target: 348
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II clinical study evaluating the safety, tolerability, pharmacokinetics and antitumor efficacy of AK146D1 in combination with AK112 or other anticancer therapies in patients with advanced Non-Small Cell Lung Cancer.

Conditions

Advanced Non Small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (3)

• Number of participants with dose limiting toxicities (DLTs)

  DLTs are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug.

  During the first 3 weeks of treatment in Safety Run-in Phase.

• Number of participants with adverse events (AEs)

  AEs refer to any untoward medical occurrence or deterioration of existing medical events after the participants sign the ICFs, whether or not considered related to the study treatment.

  From the time of signing informed consent form through 30 days(for AEs) or 90 days(for SAEs) after the last dose of study drug.

• Objective Response Rate (ORR) assessed by investigator per RECIST v1.1

  ORR is the proportion of participants with complete response(CR) or partial response(PR) , assessed based on RECIST v1.1.

  Up to approximately 2 years.

Secondary Outcomes (7)

• Progression Free Survival (PFS) assessed by investigator per RECIST v1.1

  Up to approximately 2 years.

• Disease Control Rate (DCR) assessed per RECIST v1.1

  Up to approximately 2 years.

• Duration of response (DoR) assessed by the investigator per RECIST v1.1

  Up to approximately 2 years.

• Time to response (TTR) assessed by the investigator per RECIST v1.1

  Up to approximately 2 years.

• Overall survival (OS)

  Up to approximately 2 years.

Study Arms (3)

Arm A

EXPERIMENTAL

Participants in this group will receive AK146D1 combined with AK112 and platinum as i.v. infusion.

Drug: AK146D1 for injection; Drug: AK112 Injection; Drug: Platinum chemotherapy

Arm B

EXPERIMENTAL

Participants in this group will receive AK146D1 combined with osimertinib.

Drug: AK146D1 for injection; Drug: Osimertinib

Arm C

EXPERIMENTAL

Participants in this group will receive AK146D1 combined with AK112 as i.v. infusion.

Drug: AK146D1 for injection; Drug: AK112 Injection

Interventions

AK146D1 for injection DRUG

AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate.

Arm A; Arm B; Arm C

AK112 Injection DRUG

AK112 is a PD-1/VEGF bispecific antibody.

Arm A; Arm C

Platinum chemotherapy DRUG

Carboplatin or cisplatin will be administered.

Arm A

Osimertinib DRUG

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI).

Arm B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand and voluntarily sign the written informed consent form.
• Aged of ≥ 18 years and ≤75 years.
• ECOG PS 0 or 1.
• The expected lifespan is ≥3 months.
• Patients with histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-small cell lung cancer (NSCLC) who are not eligible for curative surgical resection and cannot receive definitive concurrent or sequential chemoradiotherapy.
• At least one measurable non-brain lesion according to RECIST v1.1.
• Have sufficient organ function.
• Females subjects must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception.

You may not qualify if:

• NSCLC mixed with a component of small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma.
• Having other active malignancies within 3 years.
• Currently participating in another interventional clinical study.
• Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
• Having received any treatment targeting Trop2 or Nectin4.
• Prior chemotherapy or antibody-drug conjugate (ADC) therapy targeting topoisomerase I inhibitors.
• Receipt of systemic anti-tumor therapy (including chemotherapy, immunotherapy, biological agents, etc.) within 4 weeks (or 5 half-lives of the drug, whichever is longer) prior to the first dose.
• Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 6.0 grade 1 or lower.
• Subjects with clinically significant cardiovascular or cerebrovascular diseases or risks.
• Subjects with active autoimmune diseases requiring systemic treatment within 2 years.
• Receipt of systemic anti-infective therapy within 2 weeks prior to the first dose.
• Known to be positive for HIV and other infections.
• Previous history of severe hypersensitivity reactions.
• Live attenuated vaccines were received within 4 weeks.
• Subjects with a history of mental illness and incapacitated or limited capacity.

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

SunYat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Interventions

Injections; osimertinib

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Ting Liu

CONTACT

+86(0760)8987 3999; clinicaltrials@akesobio.com

Li Zhang, Study Principal Investigator

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2026
• First Posted: June 25, 2026
• Study Start: July 10, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): May 30, 2029
• Last Updated: July 14, 2026

Record last verified: 2026-07

Locations

CN (1)