Phase 2 Study of Pembrolizumab and Lenvatinib in Anal Squamous Cell Cancer

NCT07680088 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU20260782
• Study Type: interventional
• Target: 17
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to see the safety and efficacy of pembrolizumab and lenvatinib in patients with anal squamous cell cancer that cannot be removed through surgery or is spread to other organs. Eligible participants should have also received some form of standard therapy previously for their advanced cancer. Participants will be required to come for a clinic visit and infusion of pembrolizumab. Lenvatinib will be taken by mouth at home based on direction provided by physicians and research team.

Conditions

Anal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate of pembrolizumab and lenvatinib combination

  To determine the objective response rate (ORR) of Pembrolizumab and Lenvatinib combination. The objective response rate is defined as the rate of CR + PR as the best response on evaluation; measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. RECIST Criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions. Progressive Disease (PD): \> 20% increase in the SLD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  From time of initial treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

Secondary Outcomes (2)

• Disease control with pembrolizumab and lenvatinib combination

  From time of enrollment/treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

• Frequency of adverse events

  From time of enrollment/treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months

Study Arms (1)

Lenvatinib + Pembrolizumab

EXPERIMENTAL

Lenvatinib 20 mg orally daily on days 1-21 Pembrolizumab 200 mg every Day 1 Intravenous every 21 days

Drug: Lenvatinib; Drug: Pembrolizumab

Interventions

Lenvatinib DRUG

20 mg orally daily on days 1-21

Lenvatinib + Pembrolizumab

Pembrolizumab DRUG

200 mg every Day 1 Intravenous every 21 days

Lenvatinib + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of anal squamous cell carcinoma.
• The participants should have inoperable local recurrence or advanced cancer (stage 4; any T, any N, M1).
• The participants should have received at least one prior line of cytotoxic chemotherapy regimen in palliative setting or have declined cytotoxic chemotherapy use or have a contraindication to receive chemotherapy. Prior use of PD-1 systemic therapy is allowed
• ECOG Performance status: 0, 1 or 2.
• Adequate organ and bone marrow function as outlined below:
• Absolute neutrophil count (ANC): ≥1500/µL
• Platelets: ≥100 000/µL
• Creatinine; creatinine clearance GFR can also be used in place of creatinine or CrCl): Creatinine ≤1.5 × ULN OR Creatinine Clearance ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
• Total bilirubin: ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
• aspartate aminotransferase (serum glutamic oxaloacetic transaminase) - AST (SGOT) and ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase) - ALT (SGPT): ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT): INR ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Female Participants
• Is not a Women Of Child Bearing Potential (WOCBP): OR
• Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Appendix D during the intervention period and for at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever date occurs last. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) during screening (for the purpose of confirming eligibility/enrollment).
• Note: If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. (WOCBP should also have a negative pregnancy test within 24 hours before the first dose of study intervention (cycle1 day 1) as described in schedule of Activities Table).

You may not qualify if:

• Has received chemotherapy within 2 weeks prior to starting study treatment.
• Has received any investigational agents for the treatment of the cancer under study within 3 weeks of start of the study.
• Has received prior radiotherapy within 3 weeks of start of study intervention or suffers from radiation-related toxicities requiring corticosteroids.
• Had a major surgery within 3 weeks prior to first dose of study interventions or has not adequately recovered from a previous major surgery or has ongoing surgical complications, in the opinion of the investigator, that would limit participation in study. Note: Adequate wound healing after major surgery must be assessed clinically by investigator or qualified designee.
• Has an uncontrolled intercurrent illness including, but not limited to, ongoing or active bacterial infection requiring systemic antibiotic, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided participants are not on steroid treatment for the CNS metastasis at least 14 days prior to first dose of study intervention. An MRI assessment of the brain may be needed during Screening if clinically indicated as per investigator.
• Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
• Has a left ventricle ejection fraction \<45% as determined by multi-gated acquisition (MUGA) or 2D echocardiogram (ECHO). Among patients with a prior known history of congestive heart failure with a low ejection fraction, then ejection fraction assessment will be performed during screening to determine eligibility.
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
• Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. NOTE: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
• Have prolongation of QTc interval to \>480 ms.
• Has a history of gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib in the opinion of the investigator.
• Has an active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Has received chronic systemic steroid therapy (exceeding 10 mg daily dose of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Conditions

Anus Neoplasms

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Study Officials

• Syed Kazmi, MD

  Associate Professor

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carrie Manwaring, BS

CONTACT

214-648-7097; carrie.manwaring@utsouthwestern.edu

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: Associate Professor, Internal Medicine

Study Record Dates

• First Submitted: June 25, 2026
• First Posted: July 2, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2030
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share