Zimberelimab Plus Lenvatinib After Progression on Prior Immune Checkpoint Inhibitors for Advanced Cervical Cancer

NCT05824468 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: B2023-098-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Although immune checkpoint inhibitors (ICIs) provide a durable response in multiple tumor types, relapse occurs in most patients with solid tumor. However, the benefits of retreatment with ICIs remains controversial. In some studies, retreatment with ICIs has exhibited encouraging efficacy in patients with solid tumors, particularly in melanoma, and non-small cell lung cancer (NSCLC). In this single arm phase 2 trial, we aimed to evaluate the efficacy and safety of the combination of anti-PD1 antibody (zimberelimab) and lenvatinib in patients with advanced cervical cancer who progressed on or after prior ICIs.

Conditions

Cervical Cancer; Cervical Carcinoma

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 cycles.

  the first 21 days of treatment

• Recommended Phase 2 dose (RP2D)

  Determine the RP2D of lenvatinib

  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 zimberelimab plus lenvatinib

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

Study Arms (1)

Zimberelimab + Lenvatinib

EXPERIMENTAL

Safety run-in phase A dose de-escalation schedule is used in this phase. Dose Level 1: zimberelimab 240 mg 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: zimberelimab 240 mg 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 phase 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 zimberelimab and lenvatinib combination. In expansion stage, zimberelimab 240 mg administered intravenously and lenvatinib PR2D will be administered.

Drug: Zimberelimab; Drug: Lenvatinib

Interventions

Zimberelimab DRUG

Injectable solution

Also known as: Anti-PD-1 antibody

Zimberelimab + Lenvatinib

Lenvatinib DRUG

Capsule

Also known as: Tyrosine Kinase Inhibitor

Zimberelimab + 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 histologically confirmed diagnosis of metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.
• Has progressed on at least one line of platinum-based systemic therapy. Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic cervical cancer; adjuvant therapy includes cisplatin given concurrent with primary radiation therapy and adjuvant chemotherapy given following the completion of concurrent chemotherapy and radiation therapy. However, adjuvant chemotherapy could be counted as one prior regimen in patients who had recurrence during or within 6 months of completion of therapy.
• Has progressed on or after treatment of prior immune checkpoint inhibitors (ICIs).
• Age ≥ 18 years and ≤ 75 years.
• Has measurable disease per RECIST v1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI); a lymph node must be ≥ 15 mm in short axis. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• 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)
• Females 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 squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma.
• Known or suspected allergy to any of study drugs.
• Prior exposure to small molecule tyrosine kinase inhibitors within the past 6 months.
• 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 an active infection requiring systemic 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.
• Recieved major surgery with 28 days before the first medication or has serious nonhealing wound, or ulcer.
• 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).
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g.
• Coagulation abnormalities (INR \> 2.0, PT \> 16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
• Has known active central nervous system metastases.
• History of another malignancy in the previous 3 years, with a disease-free interval of \<3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Patients who have undergone a bone marrow or stem-cell transplant for any malignancy are excluded.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Cetntre

Guangzhou, 510060, China

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

zimberelimab; spartalizumab; lenvatinib; Tyrosine Kinase Inhibitors

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; 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: Zimberelimab, Drug: Lenvatinib

Study Record Dates

• First Submitted: April 9, 2023
• First Posted: April 21, 2023
• Study Start: May 10, 2023
• Primary Completion: July 20, 2024
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

CN (1)