A Study of SGN-CEACAM5C in Adults With Advanced Solid Tumors

Inclusion Criteria:

1. Tumor type:

• Participants in Part A (dose escalation) and Part B (dose optimization) musthave histologically- or cytologically-confirmed metastatic or unresectablesolid 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 gastroesophagealjunction adenocarcinoma (GEJ); non-small cell lung cancer (NSCLC); orpancreatic ductal adenocarcinoma (PDAC).

• The tumor types to be enrolled in Part B will be identified by the sponsorfrom among those specified in Part A.

• Participants in Part C (dose expansion) must have one of the followinghistologically- or cytologically-confirmed metastatic or unresectable solidtumor malignancies.

• CRC (adenocarcinoma of the colon or rectum) and must have received no morethan 2 prior chemotherapy regimens for the treatment of advancedcolorectal cancer and evidence of either progressive disease orintolerance to their last regimen.

• PDAC with one or more metastatic lesions measurable by computedtomography/magnetic resonance imaging according to RECIST v1.1 criteria;and must have received no more than 1 prior chemotherapy regimen for thetreatment of advanced PDAC and evidence of either progressive disease orintolerance to that regimen.

• GC or GEJ and must have received prior platinum and fluoropyrimidine-basedchemotherapy.

• NSCLC and must have received platinum-based therapy. If eligible andconsistent with local standard of care must have received a PD-1/PD-L1inhibitor. In addition, participants with tumor genomicmutations/alterations for which approved targeted therapies are availableper local standard of care, must have received such therapies.

• Small cell lung cancer (SCLC) and must have received platinum-basedtherapy for extensive-stage disease and no more than 3 prior lines oftherapy. If eligible and consistent with local standard of care must havereceived a PD 1/PD-L1 inhibitor.

• CRC participants in Part D and Part E (bevacizumab combination therapy) musthave histologically confirmed unresectable or metastatic adenocarcinoma of thecolon or rectum. Received a maximum of 2 prior chemotherapy regimens for thetreatment of advanced colorectal cancer and had demonstrated progressivedisease 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 histologicallyconfirmed unresectable or metastatic adenocarcinoma of the colon or rectum.Must not have received a prior TOPO1 inhibitor (such as irinotecan ornanoliposomal irinotecan) in any setting. 1L cohorts: No prior chemotherapy foradvanced disease. 2L cohorts (applicable to 5FU/LV + bevacizumab combinationonly): 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 havehistologically or cytologically confirmed metastatic pancreatic ductaladenocarcinoma. One or more metastatic lesions measurable by computedtomography/magnetic resonance imaging according to Response Evaluation Criteria inSolid Tumors (RECIST) version 1.1 criteria.

> 1L PDAC participants in Part E (5FU/LV + oxaliplatin combination therapy) musthave histologically or cytologically confirmed metastatic pancreatic ductaladenocarcinoma that has not been previously treated in the metastatic setting. Oneor more metastatic lesions measurable by computed tomography/magnetic resonanceimaging according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. No prior chemotherapy for PDAC with the following exception: Patientswho received adjuvant/neoadjuvant chemotherapy and who had recurrence more than 12months after completion of adjuvant/neoadjuvant chemotherapy are eligible.

2. Participants enrolled in the following study parts should have a tumor site that isaccessible for biopsy(ies) and agree to biopsy(ies) and/or submission of archivaltissue:

• Monotherapy dose optimization (Part B)

• Monotherapy (Part C) and combination therapy (Part E) disease-specificexpansion cohorts

3. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

4. Measurable disease per Response Evaluation in Solid Tumors (RECIST) v1.1 atbaseline.

Exclusion Criteria:

1. Previous exposure to CEACAM5-targeted therapy.

2. Prior treatment with a TOPO1-targeting ADC (CPT payload), such as Enhertu (trastuzumab deruxtecan) or Trodelvy (sacituzumab govitecan).

3. History of another malignancy within 3 years before the first dose of studyintervention, or any evidence of residual disease from a previously diagnosedmalignancy.

4. Active cerebral/meningeal disease related to the underlying malignancy. Participantswith a history of cerebral/meningeal disease related to the underlying malignancyare allowed if prior central nervous system disease has been treated and theparticipant is clinically stable (defined as not having received steroid treatmentfor symptoms related to cerebral/meningeal disease for at least 2 weeks prior toenrollment and with no ongoing related AEs).

> Criteria related to bevacizumab administration (participants in Parts D and E)

5. History of allergic reactions or hypersensitivity to bevacizumab or any of itsexcipients.

6. History of hypersensitivity to Chinese Hamster Ovary cell products or otherrecombinant human or humanized antibodies.

7. Serious non-healing wound, non-healing ulcer, or non-healing bone fracture.

8. Deep venous thromboembolic event within 4 weeks prior to enrollment

9. Known coagulopathy that increases risk of bleeding, bleeding diatheses.

10. History of any life-threatening VEGF-related adverse event