About the study

The study will evaluate the preliminary efficacy of 3 combinations (Sym021+Sym022, Sym021+Sym023 and Sym021+Sym023+irinotecan) in patients with biliary tract carcinomas (BTC) and with esophageal squamous cell carcinoma (ESCC) by assessing overall response rates (ORRs) per Investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 The study will also evaluate the safety and tolerability profile of the 3 combinations

Who can take part?

You may be eligible to participate in the study if you meet the following criteria:

Inclusion criteria

For Sub

1. Patients with locally advanced or metastatic biliary tract carcinoma including adenocarcinoma of the intra
2. and/or extra-hepatic bile ducts and gallbladder carcinoma. Patients with ampullary cancers are excluded.
3. Patients must only have received and progressed on or be intolerant of first-line gemcitabine and platinum-based chemotherapy in metastatic/advanced setting and should not have received prior anti-PD-(L)1 therapy. Patients with known fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement, or isocitrate dehydrogenase 1 (IDH1) mutation will be excluded. Prior anti-PD-(L)1 therapy may be allowed during the trial if regulatory approval for such therapy is obtained while this trial is enrolling.-study 3:
4. Patients with with locally advanced or metastatic esophageal squamous cell carcinoma
5. Patients must only have received and progressed on or be intolerant of first-line platinum-based chemotherapy in metastatic/advanced setting and should have received prior anti-PD-(L)1 therapy. Patients with mixed adenosquamous histology cancers are excluded. For all Sub-studies :
6. Patients with measurable disease according to RECIST v1.1
7. Patients with an ECOG PS of 0 or 1, and anticipated life expectancy of ≥3 months
8. Patients must have adequate organ function as indicated by laboratory values
9. Adequate contraception required as appropriate

Exclusion criteria

1. Patients with central nervous system (CNS) malignancy, untreated or unstable metastases
2. Patients with significant cardiovascular disease
3. Patients with
4. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to the first study drug dose
5. Active uncontrolled bleeding or a known bleeding diathesis
6. Patients with a significant pulmonary disease or condition
7. Patients with a current or recent (within 6 months) significant gastrointestinal disease or condition
8. Patients with Gilbert's syndrome or patients with UGT1A1*28 homozygosity (also known as UGT1A1 7/7 genotype)
9. Patients with a significant ocular disease or condition
10. Patients with an active, known or suspected autoimmune disease
11. Patients with any other serious/active/uncontrolled infection
12. Patients with a history of organ transplantation
13. Patients with human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active infection with hepatitis B virus or hepatitis C virus
14. Prior therapy with irinotecan
15. For Sub-study 1 and Sub-study 2: Anti-PD-(L)1, anti -LAG-3* or anti-TIM-3 containing regimen, or combination with any other systemic or localized therapy or any other immuno-oncology (IO) therapies.
16. For Sub-study 3: Anti-TIM-3 containing regimen, or combination with any other systemic or localized therapy or any other IO therapies (other than anti-PD-(L)1 agents).
17. Patients must not be on warfarin, if they have a history of acute immune-related thrombocytopenia; patients must not be on strong cytochrome P450 (CYP) 3A4 inducers, strong CYP3A4 inhibitors, or strong UGT1A1 inhibitors.
18. Patients with a known or suspected hypersensitivity to any of the excipients of formulated study drug
19. Patients with unresolved >Grade 1 toxicity associated with any prior antineoplastic therapy
20. Sub-study 1 and Sub-study 2: Patients with known FGFR2 fusion or rearrangement, or IDH1 mutation.
21. For Sub-study 3: Patients with a history of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy.

For a full list of inclusion/exclusion criteria, please visit ClinicalTrials.gov

Study locations

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How to apply

Determine if a study site for this clinical trial is near you. Contact the study to apply.