A Multicenter, Randomized, Double-Blind, Active Comparator-Controlled, Adaptive Phase 2/3 Study to Evaluate the Safety and Efficacy of EIK1001 and Pembrolizumab Versus Placebo and Pembrolizumab as First-Line Therapy in Participants with Advanced Melanoma (TeLuRide-006)

Prior treatment

• There is either chronic treatment with systemic steroids, other immunosuppressive medication, or either of these has been administered within 14 days of start of study treatment. Note: Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections are eligible. Steroid replacement for adrenal insufficiency is also permitted.
• There is a positive test result for hepatitis B virus (HBV) or HCV indicating presence of virus (it is expected that all participants will have been serologically tested for hepatitis B in advance of this study, with HBsAG, anti-HBc IgG, and anti-HBs as per ASCO 2020 Provisional Clinical Opinion [PCO] on universal Serologic testing for hepatitis B at the onset of anticancer therapy; screening should also include an anti-HCV test prior to start of cancer treatment:
• Is currently enrolled in or has recently participated in a study of an IMP and received an IMP within 4 weeks or 5 half-lives (whichever is shorter) of administration of EIK1001 or placebo.
• Participant is currently receiving medications known to be strong inhibitors or inducers of CYP3A4 and CYP1A2.
• Prior to the 1St dose of EIK1001 or placebo, the prospective participant has received systemic therapy for advanced melanoma. Note: prior adjuvant or neoadjuvant melanoma therapies (such as anti-PD-1 or anti CTLA 4 therapies or BRAF/MEK inhibitors) are permitted if all related AEs have either returned to Baseline or stabilized, with a minimum of 6 months between the last 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 study treatment.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate if they are clinically stable for at least 4 weeks with no evidence of new or enlarging brain metastases. There must be no need for immunosuppressive doses of glucocorticoids for at least 2 weeks prior to study treatment administration.

Other illness

• 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 as long as no systemic treatment is required.
• There is a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• There are any active infections requiring therapy.
• There is uncontrolled human immunodeficiency virus (HIV) infection. HIV-infected participants with well-controlled HIV may enroll.
• Known psychiatric or substance abuse disorder that would interfere with cooperation with study requirements.
• There is a known history of regular illicit drug use and/or recent history (within the last year) of substance abuse (including alcohol).
• Has a known history of prior malignancy, unless the participant has undergone potentially curative therapy with no evidence of disease recurrence for 5 years.

Lab values

• There is a history or clinical evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study or interfere with the participant’s participation for the full duration of the study

Other

• Has melanoma of ocular origin.
• Participant is pregnant, breastfeeding, or planning to conceive or father children within the projected duration of the study.
• There is a mean resting QTcF > 470 ms on triplicate electrocardiograms

• Be ≥ 12 years of age on the day of signing of informed consent/assent.
• Have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication (applies to WOCBP).
• Female participants who are WOCBP: Willing to use either 2 highly effective methods of contraception, or 1 highly effective method plus one effective method of contraception, or be willing to abstain from heterosexual activity throughout the study (Visit 1 until 120 days after the last dose of study therapy).
• All participants including adolescents must be ≥ 40 kg
• Male participants who are sexually active with a WOCBP must agree to use condoms with all WOCBP partners or abstain from heterosexual activity, during study (Visit 1 until 120 days after last dose of study drug). Also, nonpregnant WOCBP should use a highly effective contraception method during study. Male participants with pregnant partner must use condoms until 1 week after study drug discontinuation. Male participants cannot donate sperm for 120 days after last dose of study drug
• Be willing and able to provide written, informed consent/assent for the study.
• Have a life expectancy of at least 3 months.
• Have histologically or cytologically confirmed Stage 3 (unresectable) or Stage 4 metastatic melanoma per AJCC 8th ed. and be eligible for standard therapy with pembrolizumab.
• Have at least 1 lesion with measurable disease at Baseline by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by assessment of local site Investigator/radiologist.
• Have known BRAF V600 mutation status or consent/assent to BRAF V600 mutation testing per local institutional standards during the Screening Period
• Have an ECOG Performance Status of 0 to 1 for participants ≥ 18 years of age, Lansky Performance score (LPS) score ≥ 50 (for participants 12 to 15), or Karnofsky Performance Status (KPS) score ≥ 50 for participants 16 to < 18 years of age.
• Have adequate organ and marrow function as defined by normal CBC, coagulation, serum chemistry and liver function tests on specimens collected within 10 days of treatment start.