Different Doses of BI-1607 in Combination with Pembrolizumab and Ipilimumab, in Participants with Unresectable or Metastatic Melanoma

Inclusion Criteria:

1. Is willing and able to provide written informed consent for the trial.

2. Is ≥ 18 years of age on the day of signing informed consent.

3. Has histologically confirmed advanced melanoma (unresectable or metastatic melanoma)with established disease progression.

4. Participants must have progressed on treatment with an anti-PD-1/L1 mAb. Subjectswith uveal melanoma are not required to have received any prior anti-PD-1/L1treatment. PD-1 treatment progression is defined by meeting all of the followingcriteria:

5. Has received at least 2 doses of an approved anti-PD-1/L1 mAb.

6. Has demonstrated disease progression after anti PD-1/L1 as defined by RECISTv1.1.The initial evidence of disease progression is to be confirmed by a secondassessment no less than four weeks from the date of the first documenteddisease progression, in the absence of rapid clinical progression.

7. Progressive disease has been documented within 12 weeks from the last dose ofanti-PD-1/L1 mAb.

8. Participants may have received previous treatment with BRAF inhibitors alone or incombination with mitogen extracellular kinase (MEK) inhibitors.

9. Has at least 1 measurable disease lesion as defined by RECIST v1.1 criteria.

10. Must be willing to provide tumour biopsies as specified in the schedule ofassessments (SoA) unless otherwise discussed and agreed with the Sponsor in case abiopsy cannot be taken for a medical/safety reason.

11. Has a life expectancy of ≥ 12 weeks.

12. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

13. Has adequate organ function as confirmed by laboratory values

14. Participants who are hepatitis B surface antigen (HBsAg) positive are eligible ifthey have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeksand have undetectable HBV viral load prior to enrolment.

15. Participants with history of hepatitis C virus (HCV) infection are eligible if HCVviral load is undetectable at Screening.

Exclusion Criteria:

1. Has previously been treated with an anti-CTLA-4 mAb or anti-LAG3 mAb (anti-Lymphocyte Activation Gene 3).

2. Has received any prior immunotherapy and was discontinued from that treatment due toa Grade 3 or higher irAE (except endocrine disorders that can be treated withreplacement therapy) or was discontinued from that treatment due to Grade 2myocarditis or recurrent Grade 2 pneumonitis.

3. Has received the following:

4. Chemotherapy or small molecule products within 4 weeks of first dose ofBI-1607.

5. Radiotherapy within 2 weeks of first dose of BI-1607, or has radiation-relatedtoxicities, requiring corticosteroids. Participants who have previously hadradiation pneumonitis are not allowed.

6. Immunotherapy or biological anti-cancer therapy or an investigational agent oran investigational device within 4 weeks prior to the first dose of BI-1607.

7. Has not recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline.

8. Has had major surgery from which the participant has not yet recovered or isscheduled to have major surgery < 28 days prior to the first dose of trialintervention.

9. Has received a live or live-attenuated vaccine within 30 days prior to the firstdose of trial intervention.

10. Is participating or planning to participate in another interventional clinical trialor has participated in a trial of an investigational agent or has used aninvestigational device within 4 weeks prior to first dose of trial intervention.

11. Has history of allogeneic tissue/solid organ transplant.

12. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days prior the first dose of trial intervention .

13. Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years.

14. Has known active CNS metastases and/or carcinomatous meningitis.

15. Has severe hypersensitivity to (≥ Grade 3) to pembrolizumab and/or any of itsexcipients. Has known or suspected hypersensitivity to BI-1607, ipilimumab or any oftheir excipients. Previous isolated infusion related reactions (IRRs) are not to beconsidered a reason for exclusion unless Grade 4 in severity.

16. Has an active autoimmune disease that has required systemic treatment in past 2years.

17. Has a history of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids or has current pneumonitis/interstitial lung disease.

18. Is at high medical risk because of non-malignant systemic disease including severeactive infections on treatment with antibiotics, antifungals, or antivirals.

19. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testingis required unless mandated by local health authority.

20. Has cardiac or renal amyloid light-chain amyloidosis.

21. Is a female participant and has the possibility to become pregnant (or alreadypregnant or lactating/breastfeeding). However, those female participants who have anegative serum or urine pregnancy test before enrolment and agree to use a highlyeffective method of birth control for 4 weeks before entering the trial, during thetrial, and for 12 months after last dose of BI-1607 OR 4 months after the last doseof pembrolizumab, whichever is later are considered eligible.

22. Is a male participant with partner(s) of childbearing potential (unless he agrees touse a barrier method of contraception with the female partner(s) who are using onehighly effective method of contraception during the trial and for 12 months aftercompleting treatment).

23. Has uncontrolled or significant cardiovascular disease

24. Has a history or there is current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the trial, interfere with theparticipant's participation for the full duration of the trial, or in the opinion ofthe treating Investigator is not in the best interest of the participant toparticipate.

25. Has a known psychiatric or substance abuse disorder that would interfere with theparticipant's ability to cooperate with the requirements of the trial.