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

• CRB-701 (Drug): CRB-701 3.6mg/Kg administered intravenously every 21 days (Q3W)
• capcitabine (Drug): 1250 mg/m2 twice daily on days 1-14 of each 21-day cycle
• Cetuximab (EGFR inhibitor) (Drug): 400mg/m2 loading dose followed by 250mg/m2 weekly as an IV infusion or 500mg/m2 every 2 weeks.
• Docetaxel (Drug): 75 mg/m2 as an IV infusion on day 1 of each 21-day cycle or 30 mg/m2 weekly to escalate to 40 mg/m2, if tolerated.

Primary outcomes

• Objective Response Rate (%) [Up to 24 months]: Measured using RECIST version 1.1 by Blinded Independed Central Review (BICR)
• Overall Survival (months) [Approximately 3 years from randomization]: Median time to death from any cause

Secondary outcomes

• Progression Free Survival (Months) [up to 24 months from randomization]: Median time to radiographic progression per RECIST 1.1 as assessed by BICR
• Duration of Response (Months) [Up to approximately 2 years]: Duration of response to intervention as measured by RECIST 1.1 and assessed by BICR
• Change in baseline in EORTC QLQ-C30 functional and symptom scales [up to approximately 2 years]: Change from baseline in functional and symptom scales on the EORTC QLQ-C30 questionnaire. All individual functions and symptoms are measured on a scale ranging 1-4. In the functional scales a higher score represents better functioning and health. With the symptom scales a higher score represents a more severe symptom and poor health. A total score of 0-100 is derrived from the raw scores with a higher score indicating better health
• Objective Response Rate (%) [Up to approximate 2 years]: Proportion of participants that respond to treatment by RECIST 1.1 assessed by Investigator
• Time to Response (days) [up to approx 2 years]: Median time to response as measured by RECIST 1.1 and asssessed by BICR
• Time to Response (days) [up to approximately 2 years]: Time to response as measured by RECIST v 1.1 as assessed by Investigator
• Number of participants experiencing a treatment emergent adverse events [Up to approximately 2 years]: Total number of participant experiencing adverse events per treatment group irrespective of relationship to study treatment.
• Number of participants experiencing a serious treatment emergent adverse event [Up to approximately 2 years]: Number of participants who experienced a serious treatment emergent adverse events per treatment group irrespective of relationship to treatment.
• Number of participants that had a treatment modification due to an adverse event [Up to approx. 2 years]: Number of participants that had a treatment modification due to an adverse event per treatment arm. Dose modifications include dose reductions and treatment delays.
• Number of participants who discontinued study treatment due to a treatment emergent adverse event [Up to approximately 2 years]: Number of participants who discontinued study treatment due to a treatment adverse event per treatment group, irrespective of relationship to the study treatment.

Sex: All, ages: 18 Years to any

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

11 more sites not listed.

• Cesar Peres, MD, Principal investigator, Florida Cancer Specialists and Research Institute and Sarah Cannon Research Institute
• Pablo Nenclares, MD, Principal investigator, Barts & The London NHS Trust
• Ari Rosenberg, MD, Study chair, University of Chicago