Clinical trial NCT06697301: Safety and Efficacy of EIK1001-006 in Combo With Pembro Versus Placebo and Pembro as First-Line Therapy in Patients With Advanced Melanoma.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Advanced Melanoma
Keywords: Metastatic
Advanced
Lead sponsor: Eikon Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-11-20
Enrollment: 740
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is for patients with advanced melanoma who are eligible for standard therapy with Pembrolizumab.

Detailed description: This is 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. The study includes dose optimization and expansion parts.

Eligibility criteria: 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 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 to BRAF V600 mutation testing per local institutional standards during the screening period
* Have completed prior radiotherapy at least 2 weeks prior to study treatment administration.
* Have an ECOG Performance Status of 0 to 1.
* 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.
* Have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication (applies to women of childbearing potential \[WOCBP\]).
* Be willing to use either 2 adequate methods of contraception, 1 adequate method plus a hormonal method of contraception, or be willing to abstain from heterosexual activity throughout the study (Visit 1 to 120 days after the last dose of study therapy; 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 1 to 120 days after the last dose of study therapy; applies to sexually active male participants 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 and received an IMP within 4 weeks or 5 half-lives (whichever is shorter) of administration of EIK1001 or placebo.
* 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 a known history of prior malignancy, unless the participant has undergone potentially curative therapy with no evidence of disease recurrence for 5 years.
* 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.
* 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 as long as no systemic treatment is required.
* 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 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.
* 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:
* 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
* 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).
* Participant is pregnant, breastfeeding, or planning to conceive or father children within the projected duration of the study.
* Participant is currently receiving medications known to be strong inhibitors or inducers of CYP3A4 and CYP1A2.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: up to 5 years
measure: Overall survival (OS)
timeFrame: up to 5 years
measure: Objective Response (OR) (Dose Optimization Only)
timeFrame: up to 5 years
measure: Adverse Events (AEs) (Dose Optimization Only)
timeFrame: up to 2.5 years
Secondary outcomes:
measure: Adverse Events (AEs) and Discontinuation of study treatment due to any AE.
timeFrame: up to 2.5 years
measure: Objective Response (OR)
timeFrame: up to 5 years
measure: Duration of Response (DOR).
timeFrame: up to 5 years
measure: Progression Free Survival (PFS)
timeFrame: up to 5 years
measure: Objective Response (OR)
timeFrame: up to 5 years
measure: Duration of Response (DOR)
timeFrame: up to 5 years
measure: Duration of Response (DOR) (Dose Optimization Only).
timeFrame: up to 5 years
measure: Progression-free survival (PFS) per RECIST 1.1 by Investigator (Dose Optimization Only).
timeFrame: up to 5 years
measure: Overall survival (OS) (Dose Optimization Only)
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Los Angeles
country: United States
facility: The Oncology Institution of Hope and Innovation
state: California
city: Colorado Springs
country: United States
facility: UCHealth Memorial Hospital Central
state: Colorado
city: Hialeah
country: United States
facility: Bioresearch Partner
state: Florida
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center(UPMC)-Hillman Cancer Center
state: Pennsylvania
city: Wollongong
country: Australia
facility: Cancer Care Wollongong
state: New South Wales
city: Chermside
country: Australia
facility: Icon Cancer Centre Chermside
state: Queensland
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
state: Nord Jutland
city: Saxony
country: Germany
facility: Universitat Leipzig
state: Leipzig
city: Buxtehude
country: Germany
facility: Elbe Kliniken Stade-Buxtehude
state: Lower Saxony
city: Mainz
country: Germany
facility: University of Mainz Medical Center
state: RLP
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
affiliation: Eikon Therapeutics
name: Etah Kurland
role: STUDY_DIRECTOR
affiliation: Eikon Therapeutics
name: Wale Akinseli
role: STUDY_DIRECTOR
References: