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Anal Squamous Cell CarcinomaPhase 2NCT07680088

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

A Phase 2 study testing Lenvatinib and Pembrolizumab in people with Anal Squamous Cell Carcinoma, run by University of Texas Southwestern Medical Center.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Anal Squamous Cell Carcinoma
What is being tested?
Lenvatinib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
No sites listed yet
Study dates
30 Sep 2026to 30 Sep 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • A participant will be eligible for inclusion in the study if the participant:
  • 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).
  • Male Participants
  • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of lenvatinib:
  • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
  • Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below and in Appendix D:
  • Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
  • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
  • Please note that 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed.
  • Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Archival tumor tissue sample or fresh core biopsy of a tumor lesion is available. In a situation where a safe and suitable site for a fresh biopsy is not feasible and an archival tissue is not available; patients may still be eligible to enroll after discussing with UTSW PI.
  • Have adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week before C1D1.
  • The subject's urinary protein is < 1+ on dipstick or routine urinalysis; if urine protein > 2+, a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study.
  • Has a left ventricle ejection fraction > 45% as determined by multi-gated acquisition (MUGA) or 2D echocardiogram (ECHO). If patient is asymptomatic and there is a documented MUGA or 2D ECHO completed in the last 18 months, then this will be adequate to confirm eligibility.
  • Patients receiving therapeutic anticoagulation should be on a stable anticoagulant regimen within 14 days prior to first dose of study drug.
  • Subjects must have recovered from prior treatment-related toxicities to grade 1 or baseline (Some exception to criterion are, alopecia or clinically stable chronic toxicities that may be requiring ongoing medical management but are not affecting daily function as per investigator assessment, e.g. hypothyroidism or chemotherapy-induced neuropathy etc.).
  • Participants who have known history of HBV infection are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to C1D1.
  • Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
  • Hepatitis B screening tests are not required unless:
  • Known history of HBV infection
  • As mandated by local health authority or institution
  • Participants with known history of HCV infection are eligible if HCV viral load is undetectable at screening.
  • Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
  • Hepatitis C screening tests are not required unless:
  • Known history of HCV infection
  • As mandated by local health authority or institution
  • Participants with known history of HIV infection must have well-controlled HIV on anti-retroviral therapy (ART), defined as:
  • Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening.
  • Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening.
  • It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.
  • Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study.
  • The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers)
  • Ability to understand and the willingness to sign a written informed consent.

Who cannot join

  • 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.
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  • 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.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid).
  • Has a known additional malignancy that is progressing or has required active systemic treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (excluding carcinoma in situ of the bladder) that have undergone potentially curative therapy are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA <10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Lenvatinib or Pembrolizumab used in study.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has a concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
  • Note: Hepatitis B and C screening tests are not required unless:
  • Known history of HBV and HCV infection
  • As mandated by local health authority or institution
  • Has had an allogenic tissue/solid organ transplant.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Carrie Manwaring, BS contact

214-648-7097

carrie.manwaring@utsouthwestern.edu

About this study

Official title: A Multicenter Single-arm Phase 2 Study of Pembrolizumab and Lenvatinib in Previously Treated Inoperable or Advanced Anal Squamous Cell Cancer

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.

Read the detailed description

After signing this consent, participants will undergo a screening visit that includes a blood draw, physical exam and medical history review. Once screening is complete, and a participant is found to be eligible for the study, they 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 research team. Each visit will take approximately 3hours including clinic visit and infusion visit. Participants will also be asked to complete a diary to ensure they are taking lenvatinib pills as directed by their physician. During clinic visits, participants will be asked about side effects from therapy, any new symptoms, they will be examined and their blood pressure and other tests will be monitored throughout the study. Total study duration for most participants is expected to be approximately 6 months, however, it can be longer or shorter, depending upon whether a participant is benefitting from therapy or not, or if they are having any serious side effects from therapy.

Medical subject headings
Anus Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07680088
Study groupRoleWhat they receive
Lenvatinib + PembrolizumabExperimentalLenvatinib 20 mg orally daily on days 1-21 Pembrolizumab 200 mg every Day 1 Intravenous every 21 days
Receives: Drug: Lenvatinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Disease control with pembrolizumab and lenvatinib combination

    To describe the disease control with pembrolizumab and lenvatinib combination in refractory anal squamous cell cancers. The disease control rate as per iRECIST is defined as the rate of iCR + iPR + iSD as the best response on evaluation.

    iRECIST Criteria (Prefix "i" indicates immune responses assigned using iRECIST): iCR (Immune Complete Response): Complete disappearance of all target and non-target lesions.

    iPR (Immune Partial Response): At least a 30% decrease in the sum of diameters of target lesions.

    iSD (Immune Stable Disease): Tumors do not meet the criteria for iPR or iCPD.

    Measured: 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

  2. Frequency of adverse events

    To describe the adverse events associated with pembrolizumab and lenvatinib combination in refractory anal squamous cell cancers. 2.4.2.2 Frequency of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2026
  2. Study start30 Sep 2026 (estimated)
  3. Primary completion30 Sep 2028 (estimated)
  4. Study completion30 Sep 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07680088
Sponsor's protocol ID
STU20260782
Status last verified
Jun 2026
First submitted
25 Jun 2026
Last updated
2 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib and Pembrolizumab in people with Anal Squamous Cell Carcinoma, run by University of Texas Southwestern Medical Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 47 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Carrie Manwaring, BS (214-648-7097, carrie.manwaring@utsouthwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate of pembrolizumab and lenvatinib combination (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07680088.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.

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