An Open-label Phase 1 Study to Investigate PF-08046050 (SGN-CEACAM5C) in Adults With Advanced Solid Tumors
This clinical trial is studying advanced solid tumors. Solid tumors are cancers that start in a part of your body like your lungs or liver instead of your blood. Once tumors have grown bigger in one place but haven't spread, they're called locally advanced. If your cancer has spread to other parts of your body, it's called metastatic. When a cancer has gotten so big it can't easily be removed or has spread to other parts of the body, it is called unresectable. These types of cancer are harder to treat. Participants in this study must have cancer that has come back or did not get better with treatment. Participants must have a solid tumor cancer that can't be treated with standard of care drugs. This clinical trial uses an experimental drug called PF-08046050. PF-08046050 is a type of antibody-drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. They may also stick to some normal cells. This study will test the safety of PF-08046050 in participants with solid tumors that are hard to treat or have spread throughout the body. This study has 5 different study parts. Part A and Part B of the study will find out how much PF-08046050 should be given to participants. Part C will use the information from Parts A and B to see if PF-08046050 is safe and if it works to treat certain solid tumor cancers. Part D and E of the study, together with information from Parts A and B, will find out how much PF-08046050 should be given in combination with other anti-cancer agents. Part E will use the information from Parts A, B, and D to see if PF-08046050 is safe in combination with other anti-cancer agents and if it works to treat a certain solid tumor.
• Tumor type:
‣ Participants in Part A (dose escalation) and Part B (dose optimization) must have histologically- or cytologically-confirmed metastatic or unresectable solid tumor malignancy. Must have relapsed, refractory, or progressive disease, and should have no appropriate standard therapy available.
• Participants in Part A must have one of the following tumor types: colorectal cancer (CRC); gastric carcinoma (GC) or gastroesophageal junction adenocarcinoma (GEJ); non-small cell lung cancer (NSCLC); or pancreatic ductal adenocarcinoma (PDAC).
∙ The tumor types to be enrolled in Part B will be identified by the sponsor from among those specified in Part A.
⁃ Participants in Part C (dose expansion) must have one of the following histologically- or cytologically-confirmed metastatic or unresectable solid tumor malignancies.
• CRC (adenocarcinoma of the colon or rectum) and must have received no more than 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer and evidence of either progressive disease or intolerance to their last regimen.
∙ PDAC with one or more metastatic lesions measurable by computed tomography/magnetic resonance imaging according to RECIST v1.1 criteria; and must have received no more than 1 prior chemotherapy regimen for the treatment of advanced PDAC and evidence of either progressive disease or intolerance to that regimen.
∙ GC or GEJ and must have received prior platinum and fluoropyrimidine-based chemotherapy.
∙ NSCLC and must have received platinum-based therapy. If eligible and consistent with local standard of care must have received a PD-1/PD-L1 inhibitor. In addition, participants with tumor genomic mutations/alterations for which approved targeted therapies are available per local standard of care, must have received such therapies.
∙ Small cell lung cancer (SCLC) and must have received platinum-based therapy for extensive-stage disease and no more than 3 prior lines of therapy. If eligible and consistent with local standard of care must have received a PD 1/PD-L1 inhibitor.
⁃ CRC participants in Part D and Part E (bevacizumab combination therapy) must have histologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum. Received a maximum of 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen.
⁃ CRC participants in Part D and Part E (5FU/LV + bevacizumab and 5FU/LV + oxaliplatin + bevacizumab combination therapy) must have histologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum. Must not have received a prior TOPO1 inhibitor (such as irinotecan or nanoliposomal irinotecan) in any setting. 1L cohorts: No prior chemotherapy for advanced disease. 2L cohorts (applicable to 5FU/LV + bevacizumab combination only): 1 prior chemotherapy regimen for the treatment of advanced disease, which must have included a fluoropyrimidine and oxaliplatin.
• \> 2L PDAC participants in Part E (5FU/LV combination therapy) must have histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. One or more metastatic lesions measurable by computed tomography/magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
• \> 1L PDAC participants in Part E (5FU/LV + oxaliplatin combination therapy) must have histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma that has not been previously treated in the metastatic setting. One or more metastatic lesions measurable by computed tomography/magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. No prior chemotherapy for PDAC with the following exception: Patients who received adjuvant/neoadjuvant chemotherapy and who had recurrence more than 12 months after completion of adjuvant/neoadjuvant chemotherapy are eligible.
• Participants enrolled in the following study parts should have a tumor site that is accessible for biopsy(ies) and agree to biopsy(ies) and/or submission of archival tissue:
‣ Monotherapy dose optimization (Part B)
⁃ Monotherapy (Part C) and combination therapy (Part E) disease-specific expansion cohorts
• An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Measurable disease per Response Evaluation in Solid Tumors (RECIST) v1.1 at baseline.