Futibatinib in Combination With (Chemo)Immunotherapy in Colorectal Cancer and Other Solid Tumor Entities

Inclusion Criteria:

1. Patient* provides signed informed consent.

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

3. Patient has a histologically proven solid tumor:

• Specific for FUTURE-001: Histological or cytological confirmation of colorectaladenocarcinoma that is unresectable and/or metastatic with known RAS-, BRAF and MSI-status.

4. Specific for FUTURE-001: Patient must agree to participation in the accompanyingtranslational research program.

5. Specific for FUTURE-001: Patient did not receive previous therapy in palliativesetting (1st line situation).

6. Patient has ECOG Performance status ≤ 1.

7. Patient has adequate blood count, liver-enzymes, and renal function:

8. ANC > 1,500 cells/μL without the use of hematopoietic growth factors

9. Platelet count ≥ 100 x 109/L (>100,000 per mm3)

10. Hemoglobin ≥ 9 g/dL, transfusion allowed

11. Serum total bilirubin ≤ 1.5x institutional upper normal limit (ULN) (or < 2 xULN in case of liver involvement or Gilbert's disease)

12. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN without existing livermetastases, or ≤ 5 x UNL in the presence of liver metastases; AP ≤ 5 x ULN

13. Patients not receiving therapeutic anticoagulation must have an INR ≤ 1.5 ULNand aPTT ≤ 1.5 ULN. The use of full dose anticoagulants is allowed as long asthe INR or PTT is within therapeutic limits (according to the medical standardin the institution) and the patient has been on a stable dose foranticoagulants for at least three weeks at the time of inclusion

14. Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate ≥ 50 mL /min

15. Patient has serum calcium and phosphate levels within normal range.

16. Female patients of childbearing potential or male patients with female partners ofchildbearing potential must agree to remain abstinent (refrain from heterosexualintercourse) or use contraceptive methods that result in a failure rate of <1% peryear during the treatment period and in FUTURE-001 for at least 1 week after lastdose of futibatinib, 6 months after the last dose of chemotherapy or 4 months afterlast dose of tislelizumab, whatever is later. Male patients should refrain fromsperm donation/ cryopreservation throughout this period and male patients with apregnant partner must agree to remain abstinent or to use a condom for the durationof the pregnancy. Female patients of child-bearing potential must have a negativepregnancy test within the last 7 days prior to the start of trial therapy.

17. 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.

• There is no data that indicates a specific gender distribution. Therefore,patients are included regardless of their gender.

Exclusion Criteria:

1. Specific for FUTURE-001: Patient has curative colorectal cancer.

2. Patient received previous FGFR-addressed therapy with an FGFR inhibitor.

3. Patient has known presence of tumors other than the entity investigated in therespective cohort (FUTURE-001: colorectal cancer) or a secondary tumor other thansquamous or basal cell carcinomas of the skin or in situ carcinomas of the cervixwhich have been effectively treated. The sponsor decides to include patients whohave received curative treatment and have been disease-free for at least 5 years

4. Patient has known untreated or symptomatic CNS or leptomeningeal metastases.

5. Patient has history and/or current evidence of any of the following disorders:

6. Non-tumor related alteration of the calcium-phosphorus homeostasis that isconsidered clinically significant in the opinion of the investigator

7. Ectopic mineralization/calcification, including but not limited to soft tissue,kidneys, intestine, or myocardia and lung, considered clinically significant inthe opinion of the investigator

8. Patient receives simultaneous, ongoing systemic immunotherapy, chemotherapy, orhormone anti-cancer therapy or any other anti-cancer treatment not described in thetrial protocol (excluding palliative radiotherapy only for symptom control).

9. Patient has a stage B cirrhosis according to Child-Pugh criteria (or worse) orcirrhosis (of any grade) with a history of hepatic encephalopathy or clinicallysignificant ascites resulting from cirrhosis. Clinically significant ascites isdefined as ascites resulting from cirrhosis requiring diuretics or paracentesis.

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

11. Patient shows a ≥ grade 2 neuropathy

12. Patient takes St. Johns Wort within 6 weeks prior to initiation of study treatment

13. Patient has evidence of or any ongoing ophthalmological disorders. including but notlimited to, central serous retinopathy, macular/retinal degeneration, diabeticretinopathy, and previous retinal detachment

14. Patient has other serious illnesses or medical ailments within the last 12 monthsprior to the start of the study.

15. Patient has a known presence of an active, uncontrollable infection.

16. Patient has active disseminated intravascular coagulation.

17. Patient has any other serious concomitant or medical condition that, in the opinionof the investigator, presents a high risk of complications to the patient or reducesthe likelihood of clinical effect.

18. Patient participated in another interventional clinical study within 28 days priorto study enrollment or participation in a clinical study at the same time as thisstudy, unless it is an observational/ non-interventional study or during thefollow-up period of an interventional study.

19. Patient received treatment with any of the following within the specified time frameprior to the first dose of study treatment:

20. Major surgery within 4 weeks (surgical incision should be fully healed)

21. Radiotherapy for extended field within 4 weeks or limited field radiotherapywithin 2 weeks

22. Any investigational drug within 4 weeks

23. Female patients, who are pregnant or breast feeding or planning to become pregnantwithin 6 months after the end of treatment. Female patients of childbearingpotential must have a negative serum pregnancy test result within 7 days prior toinitiation of study treatment

24. Specific for FUTURE-001: Patient received prior treatment with PD-(L)1 or CTLA-4targeted treatment

25. Specific for FUTURE-001: Patient has any active autoimmune disease or has a historyof autoimmune disease (such as the following, but not limited to: autoimmunehepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis,vasculitis, nephritis , hyperthyroidism; patients with vitiligo; asthma that hasbeen completely remitted in childhood and does not require any intervention inadulthood can be included; patients with asthma requiring medical intervention withbronchodilators cannot be included)

26. Specific for FUTURE-001: Patient has immune deficiency or receives systemic steroidhormone therapy (> 10mg/day prednisone or other equivalents), or other form ofimmunosuppressive therapy within 2 weeks prior treatment initiation

27. Specific for FUTURE-001: Patient has history of uncontrolled infection with humandeficiency virus (HIV) or chronic infection with hepatitis B or C virus (HBV, HCV)

28. Specific for FUTURE-001: Patient has received a solid organ transplantation

29. Specific for FUTURE-001: Patient has history of interstitial lung disease