Bemarituzumab in FGFR2b+ Patients With Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction, Who Failed at Least One Prior Line of Palliative Chemotherapy

Inclusion Criteria:

1. Patient provide signed informed consent form.

2. Patient is ≥ 18 years at the time of given informed consent.

3. Patient has been diagnosed with histologically proven advanced or metastaticadenocarcinoma of the stomach or of the gastroesophageal junction, which is notamenable to potentially curative resection. Primary tumor locations will beclassified following AJCC/UICC 8th ed.

4. Patient has measurable disease or non-measurable, but evaluable disease, accordingto RECIST v1.1

5. Patient received at least one previous line of treatment, which includes afluoropyrimidine and a platinum, in the advanced setting or the patient has beenintolerable or ineligible to fluoropyrimidine and/or platinum. Neoadjuvant/adjuvanttreatment is not counted unless progression occurs <6 months after completion of thetreatment. In these cases, neoadjuvant/adjuvant treatment is counted as one line oftherapy. Note: patient allocation to cohort 3 only if patient received at least two previouslines of treatment.

6. Tumor material (archival and/or fresh) is available for centrally FGFR2b testingperformed by IHC.

• FGFR2b-selected population using 2+/3+ definition in ≥ 10% tumor cells.

7. Patients with HER2/neu-positive tumors are eligible if they received priorHER2/neu-targeted therapy.

8. Patient has an ECOG performance status ≤ 1.

9. Patient has a life expectancy > 12 weeks.

10. Patient has adequate hematological, hepatic and renal function.

11. Absolute number of neutrophils (ANC) ≥ 1.5 x 109/L

12. Platelets ≥ 100 x 109/L

13. Hemoglobin ≥ 9 g/dL (5.58 mmol/L), without transfusion support within 7 daysbefore the first dose of study treatment

14. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) (or < 2 x ULN incase of liver involvement or Gilbert's disease)

15. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN without existing liver metastases, or ≤ 5x ULN in the presence of liver metastases; AP ≤ 5 x ULN

16. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (measured by 24 h urine) ≥ 50 mL/min (i.e., if serum creatinine level is > 1.5 x ULN, then a 24-hour urinetest must be performed to check the creatinine clearance to be determined).

17. Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unlessreceiving anticoagulation therapy).

18. Female patients of childbearing potential, as defined in Section 5.1.7, or malepatients with female partners of childbearing potential must agree to remainabstinent (refrain from heterosexual intercourse) or use contraceptive methods thatresult in a failure rate of <1% (see Section 5.1.7) per year during the treatmentperiod and for at least 6 months after the last trial treatment. Male patients mustagree not to donate sperm within the same period. Male patients with a pregnantpartner must agree to remain abstinent or to use a condom for the duration of thepregnancy. Female patients of child-bearing potential must have a negative pregnancytest within the last 7 days prior to the start of trial therapy.

19. Patient is willing and able to comply with the protocol (including contraceptivemeasures) for the duration of the study including undergoing treatment and scheduledvisits and examinations including follow up

Exclusion Criteria:

1. Patient received prior treatment any selective inhibitor of the FGF-FGFR pathway orparticipated in a study that randomized to FGFR-targeted therapy/placebo.

2. Patient has known allergic / hypersensitive reactions to at least one of thetreatment components

3. Contraindication for standard of care (SOC) treatment regimen chosen by investigator (irinotecan, paclitaxel plus ramucirumab or trifluridine/tipiracil) according tospecific product information or clinical standards

4. Patient has known presence of tumors other than adenocarcinomas (e.g.,leiomyosarcoma, lymphoma) or a secondary tumor other than squamous or basal cellcarcinomas of the skin or in situ carcinomas of the cervix which have beeneffectively treated. The sponsor decides to include patients who have receivedcurative treatment and have been disease-free for at least 5 years.

5. Patient has squamous/ adenosquamous cell carcinoma of the stomach orgastroesophageal junction.

6. Patient receives simultaneous, ongoing, systemic immunotherapy, chemotherapy,hormone therapy or investigational treatment not described in the study protocol.

7. Patient receives current treatment with any anti-cancer therapy or major surgery ≤ 2weeks prior to study treatment start unless rapidly progressing disease is measured.

8. Patient receives simultaneous treatment with a different anti-cancer therapy (including investigational treatments) other than that provided for in the trial (excluding palliative radiotherapy for symptom control).

9. Patient has known untreated or symptomatic CNS or leptomeningeal metastases.Subjects with asymptomatic CNS metastases are eligible if clinically stable for ≥ 4weeks and require no intervention (including use of corticosteroids). Subjects withtreated brain metastases are eligible provided the following criteria are met:

10. Definitive therapy was completed at least 2 weeks prior to the first planneddose of trial treatment (stereotactic radiosurgery at least 7 days prior tofirst planned dose of study treatment)

11. At least 7 days prior to first dose of trial treatment: any CNS disease isclinically stable, subject is off steroids for CNS disease (unless steroids areindicated for a reason unrelated to CNS disease), and subject is off or onstable doses of anti-epileptic drugs

12. Patient has impaired cardiac function or clinically significant cardiac diseaseincluding unstable angina within 6 months before the first dose of study treatment,acute myocardial infarction < 6 months prior to the first dose of study treatment,New York Heart Association (NYHA) class II-IV congestive heart failure, uncontrolledhypertension (defined as an average systolic blood pressure > 160 mmHg or diastolic > 100 mmHg despite optimal treatment, uncontrolled cardiac arrhythmias requiringantiarrhythmic therapy other than beta blockers or digoxin, active coronary arterydisease or corrected QT interval (QTc) ≥ 470

13. Patient has evidence of or any ongoing ophthalmological disorders.

14. History of systemic disease or ophthalmologic disorders requiring chronic useof ophthalmic steroids

15. Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or are actively progressing

16. Unwillingness to avoid use of contact lenses during study treatment and for ≥ 100 days after the end of treatment

17. Recent (within 6 months) corneal surgery or ophthalmic laser treatment orrecent (within 6 months) history of, or evidence of corneal defects, cornealulcerations, keratitis, or keratoconus, or other known abnormalities of thecornea that may pose an increased risk of developing a corneal ulcer

18. Patient has a serious infection requiring oral or IV antibiotics within 14 daysprior to trial enrollment.

19. Patient has an acute or chronic infection with human deficiency virus (HIV), or anacute infection with hepatitis B or C virus (HBV, HCV). Exception: Subjects withhepatitis B surface antigen or core antibodies who achieve a sustained virologicresponse with antiviral therapy directed against hepatitis B and subjects withhepatitis C, who achieve a sustained virologic response following antiviral therapyare permitted.

20. Patient experienced severe, life-threatening, or recurrent (Grade 2 or higher)immune-mediated adverse events (AEs) or infusion-related reactions including thosethat led to permanent discontinuation while on treatment with immune-oncology agents

21. Patient received prior immunosuppressive therapy: immunosuppressive doses ofsystemic medications of > 10 mg/day of prednisone or equivalent must be discontinued ≥ 2 weeks before the first dose of study treatment. Short courses of high dosecorticosteroids and/or continuous low dose of prednisone (< 10 mg/day) arepermitted. In addition, inhaled, intranasal, intraocular, and/or joint injections ofcorticosteroids are allowed

22. Patient has evidence of any other serious concomitant or medical condition that, inthe opinion of the investigator, presents a high risk of complications to thepatient or reduces the likelihood of clinical effect.

23. Female patient is pregnant or breast feeding or planning to become pregnant withinand up to 4 months after end of treatment (if enrolled to Cohort 1) or up to 6months after the end of treatment (if enrolled to Cohort 2 or 3).