Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2).

Inclusion Criteria:

* Able to comprehend and willing to sign a written ICF for the study.

  * Are 18 years of age or older (or as applicable per local country requirements).
  * Histologically or cytologically verified, inoperable locally recurrent or metastatic SCAC.
  * No prior systemic therapy other than the following: a. Chemotherapy administered concomitantly with radiotherapy as a radiosensitizing agent is permitted.

    b. Prior neoadjuvant or adjuvant therapy if completed ≥ 6 months before study entry.
  * Has measurable disease per RECIST v1.1 as determined by local site investigator/radiology assessment. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.
  * Able and willing to provide adequate tissue sample and whole blood sample with central testing result prior to randomization. Biopsy for archival samples should have occurred within 9 months prior to randomization.
  * ECOG performance status 0 to 1.
  * If HIV-positive, then must be stable as defined by: a. CD4+ count ≥ 200/μL, b. Undetectable viral load per standard of care assay, c. Receiving antiretroviral therapy (ART/HAART) for at least 4 weeks prior to study enrollment, and have not experienced any HIV-related opportunistic infection for at least 4 weeks prior to study enrollment.
  * Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

* Has received prior PD-(L)1 directed therapy
* Has received prior radiotherapy with or without radiosensitizing chemotherapy within 28 days of Cycle 1 Day 1 except for palliative radiation (30 Gy or less) which is restricted for 14 days of Cycle 1 Day 1 (note: all toxicities associated should have resolved to Grade ≤ 1).
* Participants with laboratory outside of the protocol defined ranges.
* History of second malignancy within 3 years (with exceptions).
* Clinically significant pulmonary, cardiac, gastrointestinal or autoimmune disorders.
* Active bacterial, fungal, or viral infections, including hepatitis A, B, and C and IV antibiotic use within 7 days of Cycle 1 Day 1.
* Receipt of a live vaccine within 28 days of planned start of study therapy.
* History of organ transplant, including allogeneic stem cell transplantation.
* Known active CNS metastases and/or carcinomatous meningitis.
* Known hypersensitivity to platinum, paclitaxel, another monoclonal antibody, or any of the excipients that cannot be controlled with standard measures (eg, antihistamines, corticosteroids).
* Participant is pregnant or breastfeeding.
* Current use of protocol defined prohibited medication.
* Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v5.
* Inability or unlikely, in the opinion of the investigator, to comply with the Protocol requirements