A Study of Retifanlimab After Chemoradiation in People With Anal Cancer

Inclusion Criteria:

• Subject or legally authorized representative is willing and able to provide written informed consent.

• Age ≥ 18 on day of signing informed consent.

• Consent for use of archival tissue and blood draws for research purposes.

• Documentation of Disease

  o Patients must have pathologically confirmed anal squamous cell carcinoma.

  ° Pathology confirmation of the primary tumor at time of initial diagnosis is acceptable.

• Disease Specific Criteria

  • Patients must have MRD after completion of definitive-CRT defined as:

    • Detectable on the last day of or after completing definitive-CRT.
    • In patients with MRD within 6 months of CRT completion, patients with no overt clinical or radiographic progression will be eligible, the treatment response evolves for up to 6-months after completion of CRT. The ACT II trial demonstrated that 70% of patients with an incomplete response to CRT at 3-months achieved a clinical complete response by 6-months [18].
    • ctDNA will be assessed using Natera Signatera, a CLIA- validated tumor informed ctDNA assay, which MSK patients currently undergo baseline, on-treatment, and surveillance monitoring as standard of care.
    • As patients will not have measurable radiographic disease at time of enrollment, RECIST will not be used for study.

  • Patients must sign informed consent within 4 weeks of positive ctDNA result. The 4 weeks is considered from the date that the ctDNA resulted, and not the date it is drawn.

• Patients must have completed definitive CRT per institutional standards or as determined appropriate by the principal investigator.

• Resolution of all non-hematologic toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for hypothyroidism requiring medication, which must have resolved to Grade ≤2), alopecia, and other toxicities considered clinically nonsignificant and/or stable on supportive therapy as determined by the investigator.

  o Lymphopenia is a known side effect of CRT, which can take months to resolve [4], and is not an exclusion to eligibility.

• ECOG Performance Status of ≤ 2

• Required Organ Function

  • Adequate hematologic function defined as follows:

    • Absolute neutrophil count (ANC) ≥= 1,000 cells/mm3
    • Platelets ≥ 75,000 cells/mm3
    • Hemoglobin ≥ 9 g/dl

  • Adequate renal function defined as follows:

    • Creatinine clearance (CrCL) of ≥30 mL/min by the Cockcroft-Gault formula (Note: For agents for which renal excretion is not a major route of clearance and for which renal toxicity is not an issue, the threshold for creatinine clearance should be ≥30 mL/min.):

CrCl (mL/min) = [ (140 - Age) × Weight (kg)] / [72 × Serum Creatinine (mg/dL)], multiplied by 0.85 for females.

• Adequate hepatic function defined as follows:

  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)
  • AST and ALT ≤2.5 x institutional ULN

• Adequate cardiac function defined as follows:

  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.
  • To be eligible for this trial, patients with known congestive heart failure should be class 2B or better (see Appendix II: New York Heart Association (NYHA) Functional Classification).

Exclusion Criteria:

• Presence of metastatic or recurrent disease.

• Active infection requiring parenteral antibiotic(s).

• Known active TB (Bacillus tuberculosis) infection.

• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

• Active immune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (>10mg of prednisone or equivalent).

• Interstitial lung disease or active noninfectious pneumonitis.

• Known active CNS metastases and/or carcinomatous meningitis.

• History of allogeneic bone marrow/stem, cell, or solid organ transplant.

• Pregnant or nursing or expecting to conceive or father children within the projected duration of the trial.

  o Participants of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during study therapy and for 6 months following the completion of study therapy.

• Uncontrolled infection with human immunodeficiency virus (HIV). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load and CD4+ count >300/μL within 6 months are eligible.

• Known to be hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Patients who are receiving or who have received anti-HBV therapy and have undetectable HBV DNA prior to study entry are eligible.

• Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry.

• Receipt of a live vaccine within 28 days of planned start of study drug. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live-attenuated vaccines and are not allowed.

• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 agent.

• History of allergic reaction to the study agent(s), compounds of similar chemical or biologic composition to the study agent (s) (or any of its excipients).