Safety and Efficacy of EIK1001 in Combo With Pembro Versus Placebo and Pembro as First-Line Therapy in Patients With Advanced Melanoma.

Inclusion Criteria:

To be eligible for inclusion in this study, participants must:

• Be ≥ 18 years of age on the day of signing of informed consent.

• Have a life expectancy of at least 3 months.

• Have histologically or cytologically confirmed Stage 3 (unresectable) or Stage 4metastatic melanoma per AJCC 8th ed. and be eligible for standard therapy withpembrolizumab.

• Have at least 1 lesion with measurable disease at Baseline by CT or MRI according toResponse Evaluation Criteria in Solid Tumors (RECIST) 1.1 by assessment of localsite Investigator/radiologist.

• Have known BRAF V600 mutation status or consent to BRAF V600 mutation testing perlocal institutional standards during the screening period

• Have completed prior radiotherapy at least 2 weeks prior to study treatmentadministration.

• Have an ECOG Performance Status of 0 to 1.

• Have adequate organ and marrow function as defined by normal CBC, coagulation, serumchemistry and liver function tests on specimens collected within 10 days oftreatment start.

• Have a negative serum pregnancy test within 72 hours prior to receiving the firstdose of study medication (applies to women of childbearing potential [WOCBP]).

• Be willing to use either 2 adequate methods of contraception, 1 adequate method plusa hormonal method of contraception, or be willing to abstain from heterosexualactivity throughout the study (Visit 1 to 120 days after the last dose of studytherapy; applies to WOCBP who are not menopausal for > 2 years,post-hysterectomy/oophorectomy, or surgically sterilized).

• Agree to use an approved adequate contraceptive method throughout the study (Visit 1to 120 days after the last dose of study therapy; applies to sexually active maleparticipants with a partner who is WOCBP).

• Be willing and able to provide written, informed consent for the study.

Exclusion Criteria:

A participant is excluded from the study if any of the following criteria apply:

• Has melanoma of ocular origin.

• Is currently enrolled in or has recently participated in a study of an IMP andreceived an IMP within 4 weeks or 5 half-lives (whichever is shorter) ofadministration of EIK1001 or placebo.

• Prior to the 1St dose of EIK1001 or placebo, the prospective participant hasreceived systemic therapy for advanced melanoma.

• Note: prior adjuvant or neoadjuvant melanoma therapies (such as anti-PD-1 or antiCTLA 4 therapies or BRAF/MEK inhibitors) are permitted if all related AEs haveeither returned to Baseline or stabilized, with a minimum of 6 months between thelast dose of prior therapy and documented disease progression.

• Experienced a ≥ Grade 3 AE while receiving prior anti PD 1 therapy.

• Has had major surgery (< 3 weeks prior to the first dose).

• Has received a live-virus vaccination within 30 days of the first dose of studytreatment.

• Has a known history of prior malignancy, unless the participant has undergonepotentially curative therapy with no evidence of disease recurrence for 5 years.

• Has known active CNS metastases and/or carcinomatous meningitis. Participants withpreviously treated brain metastases may participate if they are clinically stablefor at least 4 weeks with no evidence of new or enlarging brain metastases. Theremust be no need for immunosuppressive doses of glucocorticoids for at least 2 weeksprior to study treatment administration.

• There is a mean resting QTcF > 470 ms on triplicate electrocardiograms.

• There is active autoimmune disease that has required systemic treatment in the past 2 years. The following autoimmune conditions are permitted: Type 1 diabetes,hypothyroidism (on hormone replacement), or- vitiligo, psoriasis and alopecia aslong as no systemic treatment is required.

• There is either chronic treatment with systemic steroids, other immunosuppressivemedication, or either of these has been administered within 14 days of start ofstudy treatment.

• Note: Participants with asthma that require intermittent use of bronchodilators,inhaled steroids, or local steroid injections are eligible. Steroid replacement foradrenal insufficiency is also permitted.

• There is a history of (noninfectious) pneumonitis/interstitial lung disease thatrequired steroids or has current pneumonitis/ interstitial lung disease.

• There are any active infections requiring therapy.

• There is uncontrolled human immunodeficiency virus (HIV) infection. HIV-infectedparticipants with well-controlled HIV may enroll.

• There is a positive test result for hepatitis B virus (HBV) or HCV indicatingpresence of virus (it is expected that all participants will have been serologicallytested for hepatitis B in advance of this study, with HBsAG, anti-HBc IgG, andanti-HBs as per ASCO 2020 Provisional Clinical Opinion [PCO] on universal Serologictesting for hepatitis B at the onset of anticancer therapy; screening should alsoinclude an anti-HCV test prior to start of cancer treatment:

• There is a history or clinical evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study or interfere with theparticipant's participation for the full duration of the study

• Known psychiatric or substance abuse disorder that would interfere with cooperationwith study requirements.

• There is a known history of regular illicit drug use and/or recent history (withinthe last year) of substance abuse (including alcohol).

• Participant is pregnant, breastfeeding, or planning to conceive or father childrenwithin the projected duration of the study.

• Participant is currently receiving medications known to be strong inhibitors orinducers of CYP3A4 and CYP1A2.