A Study of AK112 Monotherapy in Advanced/Metastatic Renal Cell Carcinoma

This is an open-label, single arm , Ib/II phase trial to evaluate the efficacy and safety of AK112（ivonescimab）monotherapy as first-line treatment for favourable risk advanced/metastatic renal cell carcinoma (a/m RCC).

Subjects will receive AK112 until disease progression, unacceptable toxic effects, death，a decision by the physician or patient to withdraw from the trial，or AK112 exposure over 2 years.

The study set dose exploration stage and dose expansion stage respectively. Firstly, include a few subjects for observation in dose exploration stage, and select appropriate dose to enter expansion, then continue to include more subjects to further assessment.

Study Overview

• Status: Not yet recruiting
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: AK112 monotherapy

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xinan Sheng, MD; Phone Number: +86-10-88196348; Email: doctor_sheng@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Provide written informed consent/assent for the trial.
• Be ≥18 and ≤ 75 years of age on day of signing informed consent, no matter male or female.
• IMDC favourable risk（IMDC score 0）.
• ECOG PS 0-1.
• Have estimated life expectancy of at least 3 months.
• Have histologically or cytologically confirmed diagnosis of RCC with mainly clear cell carcinoma component.
• Have received no prior systemic therapy for advanced RCC，Including but not limited to Immunotherapy, target therapy, chemotherapy, biological therapy, etc.

Note: Prior neoadjuvant/adjuvant therapies are acceptable if disease progression occurred > 6 months after last dosage of neoadjuvant/adjuvant treatment.

• Have measurable disease per RECIST v1.1 .
• Adequate organ function.
• Contraception from entering the trial，until 120 days after the last administration of the investigational drug.
• Willing to comply with the scheduled visits, treatment plans, and other requirements of the trial.

Exclusion Criteria:

• non-clear cell renal cell carcinoma，nccRCC（e.g. chromophobe, papillary)
• Has active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Subjects with diabetes type I, vitiligo, psoriasis, hypo-or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Has a known additional malignancy that has progressed or has required active treatment in the last 5 years.

Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or carcinoma in situ are not excluded.

• Eligible for surgery.
• History of severe bleeding or coagulation disorders.
• History of abdominal fistula or gastrointestinal perforation related to anti VEGF therapy.
• Has previously received systemic therapy.
• Has newly diagnosed brain metastases or known symptomatic brain metastases requiring steroids.
• Had major surgery 4 weeks prior to receiving first dose of trial treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to receiving first dose of trial treatment.
• Has an active tuberculosis and syphilitic infection.
• Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV antibodies).
• Has known active Hepatitis B (e.g., Hepatitis B surface antigen [HBsAg] reactive and HBV-DNA>2000 IU/ml) or Hepatitis C virus (e.g., HCV RNA [qualitative] is detected).
• Has been pregnant or breastfeeding.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment group; Subjects will receive AK112 (RP2D, administered intravenously，Q3W)	Drug: AK112 monotherapy; A novel PD-1/VEGF bispecific antibody; RP2D intravenously (IV)，Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR per RECIST v1.1 assessed by investigators	ORR is the proportion of subjects with complete response(CR) and partial response(PR) , based on RECIST v1.1	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	Duration of response (DOR) assessed according to RECIST v1.1	Up to 2 years
Treatment-related adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, also types and degree	3 years
DCR per RECIST v1.1 as assessed by investigators	DCR is the proportion of subjects with complete response(CR), partial response(PR) and stable disease (SD) based on RECIST v1.1	Up to 2 years
Progression-free survival (PFS)	PFS is defined as the time from the the start of treatment till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).	3 years
Overall survival (OS)	OS is the time from the first use of a therapeutic drug to death from any cause	4 years

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): July 20, 2024
• Primary Completion (Estimated): December 20, 2025
• Study Completion (Estimated): December 20, 2027

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: June 19, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 19, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: RCC，immunotherapy，AK112，first-line treatment
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: AK112-001-II-RCC

Drug and device information, study documents

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