Safety and Efficacy of EIK1001 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 (TeLuRide-006)

Overview

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.

Interventions

• Drug EIK1001
  EIK1001 is a Toll-like receptor 7/8 (TLR 7/8) dual agonist.
• Drug Pembrolizumab (KEYTRUDA® )
  Pembrolizumab is a PD-1 inhibitor.

Primary outcome measures

• Progression Free Survival (PFS) [Time frame: up to 5 years]
• Overall survival (OS) [Time frame: up to 5 years]
• Objective Response (OR) (Dose Optimization Only) [Time frame: up to 5 years]
• Adverse Events (AEs) (Dose Optimization Only) [Time frame: up to 2.5 years]

Secondary outcome measures (9)

• Adverse Events (AEs) and Discontinuation of study treatment due to any AE. [Time frame: up to 2.5 years]
• Objective Response (OR) [Time frame: up to 5 years]
• Duration of Response (DOR). [Time frame: up to 5 years]
• Progression Free Survival (PFS) [Time frame: up to 5 years]
• Objective Response (OR) [Time frame: up to 5 years]
• Duration of Response (DOR) [Time frame: up to 5 years]
• Duration of Response (DOR) (Dose Optimization Only). [Time frame: up to 5 years]
• Progression-free survival (PFS) per RECIST 1.1 by Investigator (Dose Optimization Only). [Time frame: up to 5 years]
• Overall survival (OS) (Dose Optimization Only) [Time frame: up to 5 years]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Spain · 15 centers

Center list to be confirmed — check the primary protocol.

Germany · 12 centers

• Universitätsmedizin Mannheim — Mannheim
• Universitaetsklinikum Tuebingen (UKT) — Tübingen
• Klinik für Dermatologie, Venerologie und Allergologie — Würzburg
• Universitätsklinik Hamburg Eppendorf — Martinsried
• Universitat Leipzig — Saxony
• Elbe Kliniken Stade-Buxtehude — Buxtehude
• Johannes Wesling Klinikum Minden — Minden
• University of Mainz Medical Center — Mainz
• … and 4 more centers

United States · 11 centers

• Ironwood Cancer & Research Centers — Chandler
• Genesis Cancer and Blood Institute — Hot Springs
• Helios Clinical Research — Los Angeles
• Providence Medical Foundation — Santa Rosa
• UCHealth Memorial Hospital Central — Colorado Springs
• Bioresearch Partner — Hialeah
• The Center for Cancer and Blood Disorders — Bethesda
• MidAmerica Cancer Care — Kansas City
• … and 3 more centers

France · 10 centers

• Centre Hospitalier Lyon-Sud — Pierre-Bénite
• A Paré — Boulogne
• Centre Hospitalier Universitaire Grenoble Alpes — La Tronche
• CHU Lille — Polonovski
• Hôpital La Timone — Marseille
• Centre Hospitalier Universitaire (CHU) Nice — Nice
• Hôpital Bichat AP-HP Université Paris Cité — Paris
• ICO Saint Herblain — Saint-Herblain
• … and 2 more centers

South Africa · 7 centers

• Cancercare Port Elizabeth - Langenhoven Drive Oncology Centre — Port Elizabeth
• University of Pretoria, Steve Biko Academic Hospital — Pretoria
• The Medical Oncology Centre of Rosebank — Saxonwold
• Abraham Oncology — Richards Bay
• Curo Oncology — Pretoria
• … and 2 more centers

Belgium · 6 centers

• Universitair Ziekenhuis Antwerpen — Edegem
• Cliniques Universitaires Saint-Luc — Brussels
• Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne — Yvoir
• Universitair Ziekenhuis Leuven - Campus Gasthuisberg — Leuven
• Algemeen Ziekenhuis Groeninge - Campus Kennedylaan — Kortrijk
• Vitaz Primary Location — Sint-Niklaas

Australia · 5 centers

• Cancer Care Wollongong — Wollongong
• Icon Cancer Centre Chermside — Chermside
• Southern Adelaide Local Health Network Incorporated Flinders Medical Centre — Bedford Park
• Eastern Health — Box Hill
• Peninsula and South Eastern Haematology and Oncology Group — Frankston

Israel · 4 centers

• Soroka medical center — Beersheba
• Rabin Medical Center — Petah Tikva
• Ella Lemelbaum Institute for Immuno-Oncology and Melanoma — Ramat Gan
• Tel Aviv Medical Center — Tel Aviv

Italy · 4 centers

• IRCCS Ospedale San Raffaele — Milan
• Humanitas Gavazzeni Bergamo — Bergamo
• Clinica Oncologia Delle Marche — Ancona
• UOC Immunoterapia Oncologica — Siena

Poland · 4 centers

• Uniwersyteckie Centrum Kliniczne — Gdansk
• Prezychodnia Lekarska KOMED Roman Karaszewski — Konin
• Mazowiecki Szpital Wojewódzki, Siedlckie Centrum Onkologii — Siedlce
• Maria Sklodowska-Curie National Cancer Research Institute — Warsaw

United Kingdom · 4 centers

Center list to be confirmed — check the primary protocol.

Finland · 3 centers

• Oulu University Hospital — Oulu
• Tampere University Hospital — Tampere
• Helsinki University Hospital — Helsinki

Norway · 3 centers

• Nordland Hospital Trust — Bodø
• Oslo University Hospital - The Norwegian Radium Hospital — Oslo
• Drammen Hospital — Drammen

Czechia · 2 centers

• Masaryk Memorial Cancer Institute — Brno
• University Hospital Hradec Kralove — Sokolov

Denmark · 2 centers

• Aarhus Universitetshospital — Aarhus
• Aalborg University Hospital — Aalborg

Hungary · 2 centers

• National Institute of Oncology — Budapest
• University of Pécs — Pécs

New Zealand · 2 centers

• Christchurch Public Hospital — Christchurch
• Auckland City Hospital — Auckland

Portugal · 2 centers

• IPO Lisboa — Lisbon
• Hospital da Luz Lisboa — Lisbon

South Korea · 2 centers

Center list to be confirmed — check the primary protocol.

Sweden · 2 centers

Center list to be confirmed — check the primary protocol.

Switzerland · 2 centers

Center list to be confirmed — check the primary protocol.

Austria · 1 center

• Universitätsklinikum Graz — Graz

Canada · 1 center

• Sunnybrook Research Ins<tute — Toronto

Serbia · 1 center

• Military Medical Academy- Department of Oncology — Belgrade

Identifiers

NCT: NCT06697301 · EIK1001-006 · KEYNOTE-G04 · MK-3475-G04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗