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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Non Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: AK146D1 for injection; Drug: AK112 Injection; Drug: Platinum chemotherapy; Drug: Osimertinib

• Study Type: Interventional
• Enrollment (Estimated): 348
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ting Liu; Phone Number: +86(0760)8987 3999; Email: clinicaltrials@akesobio.com
• Study Contact Backup: Name: Li Zhang, Study Principal Investigator

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • SunYat-sen University Cancer Center
      • Contact: Li Zhang; Phone Number: 020-87343009; Email: zhangli@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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. 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.
6. At least one measurable non-brain 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. NSCLC mixed with a component of small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma.
2. Having other active malignancies within 3 years.
3. Currently participating in another interventional clinical study.
4. Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
5. Having received any treatment targeting Trop2 or Nectin4.
6. Prior chemotherapy or antibody-drug conjugate (ADC) therapy targeting topoisomerase I inhibitors.
7. 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.
8. Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 6.0 grade 1 or lower.
9. Subjects with clinically significant cardiovascular or cerebrovascular diseases or risks.
10. Subjects with active autoimmune diseases requiring systemic treatment within 2 years.
11. Receipt of systemic anti-infective therapy within 2 weeks prior to the first dose.
12. Known to be positive for HIV and other infections.
13. Previous history of severe hypersensitivity reactions.
14. Live attenuated vaccines were received within 4 weeks.
15. Subjects with a history of mental illness and incapacitated or limited capacity.
16. Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Participants in this group will receive AK146D1 combined with AK112 and platinum as i.v. infusion.	Drug: AK146D1 for injection; AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate.; Drug: AK112 Injection; AK112 is a PD-1/VEGF bispecific antibody.; Drug: Platinum chemotherapy; Carboplatin or cisplatin will be administered.
Experimental: Arm B; Participants in this group will receive AK146D1 combined with osimertinib.	Drug: AK146D1 for injection; AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate.; Drug: Osimertinib; Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI).
Experimental: Arm C; Participants in this group will receive AK146D1 combined with AK112 as i.v. infusion.	Drug: AK146D1 for injection; AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate.; Drug: AK112 Injection; AK112 is a PD-1/VEGF bispecific antibody.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) assessed by investigator per RECIST v1.1	PFS is defined as the time from the start of treatment until the first documentation of disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first.	Up to approximately 2 years.
Disease Control Rate (DCR) assessed per RECIST v1.1	DCR is defined as the proportion of participants with CR, PR, or SD, assessed based on RECIST v1.1.	Up to approximately 2 years.
Duration of response (DoR) assessed by the investigator per RECIST v1.1	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first.	Up to approximately 2 years.
Time to response (TTR) assessed by the investigator per RECIST v1.1	TTR is defined as the time to objective response based on RECIST v1.1.	Up to approximately 2 years.
Overall survival (OS)	OS is defined as the time from the first dose to death from any cause.	Up to approximately 2 years.
Serum PK concentration of AK146D1 and AK112	Serum PK concentration of AK146D1 and AK112 in participants after administration.	From pre-dose to the end of the last dose, an average of 6 months.
Anti-drug antibodies (ADA)	The number and percentage of participants with detectable anti-drug antibodies (ADA)	From pre-dose to 30 days post end of treatment.

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): May 30, 2029

Study Registration Dates

• First Submitted: June 21, 2026
• First Submitted That Met QC Criteria: June 21, 2026
• First Posted (Actual): June 25, 2026

Study Record Updates

• Last Update Posted (Actual): June 25, 2026
• Last Update Submitted That Met QC Criteria: June 21, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Drug Administration Routes; Drug Therapy; Injections; osimertinib
• Other Study ID Numbers: AK146D1-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No