S095033 in Combination With Paclitaxel as 2nd- or 3rd-line Treatment in Participants With Advanced or Metastatic ESCC

Inclusion Criteria: 1. Male or female participant aged ≥ 18 years of age. 2. Estimated life expectancy ≥12 weeks. 3. Eastern Cooperative Oncology Group (ECOG) performance status \< 2. 4. Women of childbearing potential (WOCBP) must use a highly effective method of birth control during study treatment until at least 6 months after the last dose of investigational medicinal product (IMP). In case of use of oral contraception, women should have been stable on the same contraceptive drug (i.e. same active principle) for at least 3 months prior to the first IMP administration. 5. Male participants with WOCBP partners must use a condom during the study and until at least 6 months after the last dose of IMP. In addition, contraception should be considered for their female partners. Contraceptive measures do not apply if the participant is sterile, vasectomized or sexually abstinent. Sperm donation will not be allowed during the study and for 6 months after the last dose of IMP. 6. Obtained informed consent (ICF) prior to any study-specific procedure. 7. Participants with histologically confirmed advanced or metastatic esophageal squamous cell carcinoma that has failed to respond to or has progressed after treatment with standard fluorouracil and platinum-based chemotherapy, or with an anti-PD1 or PD-L1 antibody and not previously treated with a taxane. 8. Participants who have received one or two prior lines of systemic therapy. 9. Documented progression on prior line of therapy. 10. Participants must have at least one measurable lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for solid tumors. 11. For participants with MTAP deletion, evidence of homozygous loss of MTAP in archival or fresh tumor tissue. 12. For participants with MTAP wild type, evidence of the presence of MTAP in archival or fresh tumor tissue. 13. Adequate hematological function based on the last assessment performed within 7 days prior to the first IMP administration. 14. Adequate coagulation function for all participants. For participants receiving anti- coagulant therapy (except platelet anti-aggregants), the adequate therapeutic levels of INR should be confirmed. 15. Adequate renal function based on the last assessment performed within 7 days prior to the first IMP administration. 16. Adequate hepatic function based on the last assessment performed within 7 days prior to the first IMP administration. 17. Serum albumin ≥ 3 g/dL. Exclusion Criteria: 1. Non-ability to swallow oral medication. 2. Pregnant and lactating women. 3. WOCBP tested positive in a pregnancy test within 7 days prior to the first day of IMP administration. 4. Participation in another interventional study at the same time or within 2 weeks prior to the first IMP administration. 5. Participant already enrolled in the study (informed consent signed) and having received at least 1 dose of S095033 and/or paclitaxel. 6. Known prior severe hypersensitivity to investigational products or any component in their formulations. 7. Participants who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 1 non-hematologic toxicity, according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) version 5.0, prior to the first IMP administration. 8. Major surgery within 4 weeks prior to the first IMP administration or participants who have not recovered from side effects of the surgery. 9. Participants who do not have a biopsy (or sections of it) available or readily obtainable for central confirmation of MTAP status. 10. Have a history of Gilbert's syndrome. 11. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization. 12. Apparent tumor invasion into organs located adjacent to the esophageal disease site (e.g. aorta or respiratory tract) at an increased risk of fistula in the study treatment assessed by investigator. 13. Have a degenerative retinal disease that could increase the risk for visual loss with S095033 or confound the interpretation of retinal changes in the course of S095033 treatment. 14. Severe or uncontrolled active acute or chronic infection. 15. Participants with a known clinically significant cardiovascular disease or condition. 16. Participants with thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to first IMP administration. 17. Symptoms suggesting central nervous system involvement, including symptomatic metastasis, for which treatment is required. 18. Participants who have received systemic anticancer treatment or radiotherapy less than 2 weeks before the first dose of S095033. 19. Any clinically significant medical condition (e.g. organ dysfunction) or laboratory abnormality likely to jeopardize the participant's safety or to interfere with the conduct of the study, in the investigator's opinion. 20. Any contraindication to the use of paclitaxel as per standard labelling and local guidance. 21. For prior and forbidden concomitant medication.