A Study to Evaluate CRB-701 Compared to Investigator's Choice Therapy in Previously Treated Oropharyngeal Squamous Cell Carcinoma

A Randomized, 2-Arm Study to Evaluate the Efficacy and Safety of CRB-701 Compared With Investigator's Choice of Capecitabine, Cetuximab, or Docetaxel in Participants With Recurrent or Metastatic Oropharyngeal Squamous Cell Carcinoma Previously Treated With Platinum-based Chemotherapy and a PD-(L)1 Inhibitor

The goal of this study is to understand whether CRB-701, a targeted form of chemotherapy called an anti-body drug conjugate, will work as a treatment for oropharyngeal (throat, tonsil) cancer. In patients who have already received platinum based chemotherapy or immunotherapy (using a check-point inhibitor) It will also learn about the safety of the drug and measure quality of life. The main questions it asks are:

• What proportion of participants respond to CRB-701 measured using scans (CT or MRI)
• What medical problems do participants experience when taking CRB-701.

Researchers will compare CRB-701 with standard of care medicines (drugs that are normally used this disease).

Participants will:

• Attend clinic every three weeks to receive infusions of CRB-701 or standard of care medicines until the cancer cannot be measured or is not controlled by the treatment they are receiving.
• Have a CT or MRI every 6 weeks to measure the effect on their cancer
• Complete questionnaires to assess their health status.

Inclusion Criteria:

• Histological and/or cytological confirmed diagnosis of OPSCC arising from tonsils, base of tongue, soft palate and posterior pharyngeal wall, with evidence of metastatic or recurrent disease not amenable to standard therapy with curative intent.
• Either second or third-line OPSCC patients who have progressed on or after receiving SOC therapy (that must have included platinum chemotherapy and an anti-PD-(L)1 antibody administered sequentially or together) OR received platinum chemotherapy and/or anti-PD-(L)1 therapy in the neoadjuvant or adjuvant setting or as part of definitive chemoradiation therapy, provided disease recurrence occurred less than 6 months after completion of the relevant systemic therapy.
• ECOG PS of 0-1
• Measurable disease as per RECIST v1.1, with at least one measurable lesion not previously irradiated unless unequivocal progression has been documented after radiation.
• Life expectancy of greater than 12 weeks at time of enrollment, as per Investigator's assessment.

Signed informed consent

Exclusion Criteria:

• Persistent CTCAE Grade >1 clinically significant toxicities related to prior antineoplastic therapies, excluding alopecia.
• Significant active or chronic corneal disorders
• Pre-existing Grade ≥2 peripheral neuropathy
• Any other significant co-morbidities, disease, metabolic dysfunction, physical examination, or clinical laboratory finding that contraindicates the use of the investigational drug or may represent an unacceptable risk from treatment complications or may affect adherence to the study procedures or the interpretation of the results.
• Pregnant or breastfeeding females