The purpose of this trial is to evaluate how well petosemtamab in combination with chemotherapy works against colorectal cancer that has recurred after previous treatment and that cannot be safely removed by surgery or has spread to other parts of the body. Participants will receive either petosemtamab + doctor's choice of chemotherapy (mFOLFOX6 or FOLFIRI) or doctor's choice of standard-of-care (SOC) cetuximab or bevacizumab + chemotherapy (mFOLFOX6 or FOLFIRI). No participants will be given placebo. The treatment duration will be different for every participant. If a participant's cancer stays the same or gets better, and there are not any serious problems, participants can keep getting study treatment for as long as the study is open. Participants will be asked to attend 2 visits at the study clinic for each cycle (duration of cycle is 4 weeks). During visits, there will be various tests (such as blood draws) and procedures (such as imaging) to monitor whether the study treatment is safe and effective. The overall study duration (including screening, treatment, and follow-up) will be different for every participant.
This is a Phase 3, randomized, open-label, global, multicenter, interventional trial to evaluate the efficacy and safety of petosemtamab in combination with investigator's choice (IC) chemotherapy (fluorouracil + leucovorin \[calcium folinate\] + irinotecan \[FOLFIRI\] or 5-FU, leucovorin \[calcium folinate\], and oxaliplatin \[mFOLFOX6\]; Arm A) versus IC cetuximab or bevacizumab in combination with IC chemotherapy (FOLFIRI or mFOLFOX6; Arm B) as second line (2L) treatment for participants with KRAS, NRAS, and BRAF wild type (wt), recurrent, unresectable or metastatic colorectal cancer (CRC).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
600
Intravenous (IV) infusion.
IV infusion.
IV infusion.
IV infusion.
IV infusion.
IV infusion.
IV infusion.
PanOncology
Manati, Puerto Rico
RECRUITINGProgression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Central Review (BICR)
Time frame: Up to approximately 2.5 years
Objective Response Rate (ORR) per RECIST v1.1 as Assessed by BICR
Time frame: Up to approximately 2.5 years
Overall Survival (OS)
Time frame: Up to approximately 3.5 years
Duration of Response (DOR) per RECIST v1.1 as Assessed by BICR
Time frame: Up to approximately 3.5 years
Disease Control Rate (DCR) per RECIST v1.1 as Assessed by BICR
Time frame: Up to approximately 3.5 years
Progression-free Survival after First Subsequent Therapy (PFS2)
Time frame: Up to approximately 3.5 years
Curative Resection (R0) Rate
Time frame: Up to approximately 3.5 years
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to approximately 3.5 years
Change from Baseline in Symptoms and Functioning, as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire (QLQ)-F17
Time frame: Baseline up to approximately 3.5 years
Change from Baseline in Symptoms and Functioning, as Measured by EORTC QLQ-CR29
Time frame: Baseline up to approximately 3.5 years
Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-F17
Time frame: Baseline up to approximately 3.5 years
Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-CR29
Time frame: Baseline up to approximately 3.5 years
Overall Side Effect Burden, as Measured by EORTC Item 168
Time frame: Baseline up to approximately 3.5 years
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