Study of Cadonilimab (AK104) Plus Lenvatinib in Patients With Advanced Endometrial Cancer

NCT05824481 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: B2023-099-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multi-center Phase II study of cadonilimab (AK104) combined with lenvatinib in patients with advanced endometrial cancer. The primary objective is to evaluate objective response rate of cadonilimab plus lenvatinib.

Conditions

Endometrial Cancer; Endometrial Adenocarcinoma

Keywords

Endometrial Cancer; Immune Checkpoint Inhibitors (ICIs); Anti-PD-1/CTLA4 bi-specific antibody; Antiangiogenic agents; Lenvatinib

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  MTD is defined as the highest dose level at which no more than 1 out of 6 subjects experiences a dose limiting toxicities (DLT) during the first cycle.

  the first 21 days of treatment

• Recommended Phase 2 dose (RP2D)

  Determine the RP2D of lenvatnib

  the first 21 days of treatment

• Response Rate (ORR)

  ORR is the proportion of patients with best response of complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  from the first drug administration up to two years

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  from the first drug administration up to two years

• Disease Control Rate (DCR)

  from the first drug administration up to two years

• Duration of response (DOR)

  from the first drug administration up to two years

• Overall survival (OS)

  from the first drug administration up to 2 years

• Safety and tolerability

  up to 90 days after last study treatment administration

Other Outcomes (1)

• Biomarkers associated with the response to cadonilimab plus lenvatinib

  Samples taken prior to the first dose of drug, Cycle 3 and at progression

Study Arms (1)

Cadonilimab + Lenvatinib

EXPERIMENTAL

Safety run-in stage. A dose de-escalation schedule is used in this phase. Dose Level 1: cadonilimab 10 mg/kg administered intravenously on day 1 and lenvatinib 16 mg administered orally once daily on a 21-day treatment cycle. If ≥2/6 patients experience a DLT, we will de-escalate to Dose Level 2: cadonilimab 10 mg/kg administered intravenously on day 1 and lenvatinib 12 mg administered orally once daily on a 21-day treatment cycle. Approximately 3-12 patients will be enrolled in the safety run-in phase. Expansion stage. The expansion stage will begin once the RP2D of lenvatinib have been determined in the safety run-in phase in order to assess antitumor activity of cadonilimab and lenvatinib combination. In expansion stage, cadonilimab 10 mg/kg and lenvatinib PR2D will be administered.

Drug: Cadonilimab; Drug: Lenvatinib

Interventions

Cadonilimab DRUG

Injectable solution

Also known as: AK104

Cadonilimab + Lenvatinib

Lenvatinib DRUG

Capsule

Also known as: Tyrosine Kinase Inhibitor

Cadonilimab + Lenvatinib

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form (ICF).
• Has a histologically confirmed diagnosis of endometrial carcinoma (EC). Has documented evidence of metastatic or recurrent EC which is not amenable to curative treatment with surgery and/or radiation therapy.
• Failure or intolerance of standard first-line platinum-based chemotherapy regimen for EC.
• Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of advanced EC. However, adjuvant chemotherapy could be counted as one prior regimen in patients who had recurrence during or within 12 months of completion of therapy. There is no restriction regarding hormonal therapy.
• Age ≥ 18 years and ≤ 75 years.
• Has measurable disease per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy exceeds 3 months.
• Has adequate organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) (≥1.5×109/L), hemoglobin of ≥90 g/L, platelets ≥100 ×109/L
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 × ULN may be enrolled)
• Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula)
• \. Women of childbearing potential should have a negative serum or urine pregnancy test prior to receiving the first dose of study treatment; and should be willing to use one acceptable contraception (i.e., oral contraceptives, condoms, intrauterine devices \[IUDs\]) throughout the period of taking study treatment and for at least 6 months after the last dose of study drug(s).

You may not qualify if:

• Histologic types of carcinoma other than endometrial carcinoma.
• Known or suspected allergy to any of study drugs.
• Prior exposure to any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or small molecule anti-angiogenic agent.
• Has an active autoimmune disease requiring systemic therapy (i.e., with use of disease modifying drugs, corticosteroids or immunosuppressive drugs) in past 2 years. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted.
• Concurrent medical condition requiring the use of systemic steroid therapy (dose \>10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to the first dose of study intervention.
• Has received anti-tumor treatment within 28 days, including but not limited to chemotherapy and radiotherapy or targeted therapy.
• Any unresolved toxicities from prior therapy, greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with exception of alopecia and anemia.
• Has an active infection requiring systemic therapy.
• Clinically significant cardiovascular diseases, including but not limited to congestive heart failure (New York heart association \[NYHA\] class \>2), unstable or severe angina, severe acute myocardial infarction within 6 months before enrollment, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.
• Hypertension that can not be well controlled through antihypertensive drugs (systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg).
• Received major surgery with 28 days before the first medication.
• Coagulation abnormalities (INR \>2.0, PT \>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
• Proteinuria ≥ (++) or 24 hours total urine protein \>1.0g.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
• Has known active hepatitis B disease (hepatitis B virus \[HBV\] DNA ≥1×104/ml) or hepatitis C disease (hepatitis C virus \[HCV\] RNA ≥1×103/ml).

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Cetntre

Guangzhou, 510060, China

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

lenvatinib; Tyrosine Kinase Inhibitors

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: Drug: Cadonilimab Drug: Lenvatinib

Study Record Dates

• First Submitted: April 9, 2023
• First Posted: April 21, 2023
• Study Start: May 8, 2023
• Primary Completion: July 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

CN (1)