Clinical trial NCT06472895: A Study of AK112 Monotherapy in Advanced/Metastatic Renal Cell Carcinoma
Official title: A Study of AK112 Monotherapy in Advanced/Metastatic Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Renal Cell Carcinoma
Keywords: RCC，immunotherapy，AK112，first-line treatment
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2024-06-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: ORR per RECIST v1.1 assessed by investigators
timeFrame: Up to 2 years
Secondary outcomes:
measure: DCR per RECIST v1.1 as assessed by investigators
timeFrame: Up to 2 years
measure: Duration of response (DOR)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: 3 years
measure: Overall survival (OS)
timeFrame: 4 years
measure: Treatment-related adverse events
timeFrame: 3 years
Other outcomes:
Locations:
Study officials:
References: