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

Sponsor-declared trial summary

Key facts

Sponsor

Eikon Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Mar 2025 → ongoing

Decision date (initial)

2025-01-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Eikon Therapeutics, Inc.

External identifiers

EU CT number

2024-512659-19-00

ClinicalTrials.gov

NCT06697301

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Efficacy, Dose response, Pharmacokinetic, Therapy

1. To evaluate efficacy and safety various doses of EIK1001 in combination with pembrolizumab (Dose Optimization).
2. To compare progression-free survival (PFS) of EIK1001 + pembrolizumab to placebo + pembrolizumab according to RECIST 1.1 by blinded independent central review (BICR)
o Hypothesis (H1): EIK1001 + pembrolizumab prolongs PFS compared to placebo + pembrolizumab.
3. To compare overall survival (OS) of EIK1001 + pembrolizumab to placebo + pembrolizumab
o Hypothesis (H2): EIK1001 + pembrolizumab prolongs OS compared to placebo + pembrolizumab.

Secondary objectives 5

1. To evaluate the safety and tolerability of EIK1001 Selected Dose + pembrolizumab compared with placebo + pembrolizumab.
2. To evaluate objective response rate (ORR) and duration of response (DOR) according to RECIST 1.1 by BICR.
3. To evaluate PFS, ORR, and DOR according to RECIST 1.1 as assessed by the Investigator.
4. To evaluate DOR according to RECIST 1.1 as assessed by the Investigator (Dose Optimization).
5. To evaluate PFS according to RECIST 1.1 as assessed by the Investigator and OS (Dose Optimization) Note: it is not part of dose selection interim analysis.

Conditions and MedDRA coding

Advanced Melanoma

Study design 3 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000000-PIP00-00

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Be ≥ 12 years of age on the day of signing of informed consent/assent.
2. 2. Have a life expectancy of at least 3 months.
3. 3. 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.
4. 4. 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.
5. 5. Have known BRAF V600 mutation status or consent/assent to BRAF V600 mutation testing per local institutional standards during the Screening Period
6. 6. 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.
7. 7. 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.
8. 8. Have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication (applies to WOCBP).
9. 9. 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).
10. 10. 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).
11. 11. Be willing and able to provide written, informed consent/assent for the study.

Exclusion criteria 20

1. Has melanoma of ocular origin.
2. 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.
3. 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.
4. Experienced a ≥ Grade 3 AE while receiving prior anti PD 1 therapy.
5. Has had major surgery (< 3 weeks prior to the first dose).
6. Has received a live-virus vaccination within 30 days of the first dose of study treatment.
7. Has a known history of prior malignancy, unless the participant has undergone potentially curative therapy with no evidence of disease recurrence for 5 years.
8. 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.
9. There is a mean resting QTcF > 470 ms on triplicate electrocardiograms
10. 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.
11. 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.
12. There is a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
13. There are any active infections requiring therapy.
14. There is uncontrolled human immunodeficiency virus (HIV) infection. HIV-infected participants with well-controlled HIV may enroll.
15. 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:
16. 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
17. Known psychiatric or substance abuse disorder that would interfere with cooperation with study requirements.
18. There is a known history of regular illicit drug use and/or recent history (within the last year) of substance abuse (including alcohol).
19. Participant is pregnant, breastfeeding, or planning to conceive or father children within the projected duration of the study.
20. Participant is currently receiving medications known to be strong inhibitors or inducers of CYP3A4 and CYP1A2.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Objective Response (OR; defined as participants who demonstrate confirmed complete response [CR] or partial response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 as assessed by the Investigator), adverse events (AEs), and discontinuation of study treatment due to an AE (Dose Optimization).
2. PFS defined as the time from randomization to documented progressive disease per RECIST 1.1 by BICR or death due to any cause, whichever occurs first.
3. OS defined as the time from randomization to death due to any cause

Secondary endpoints 5

1. AEs and discontinuation of study treatment due to any AE.
2. OR and DOR; OR defined as participants who demonstrate confirmed CR or PR; DOR defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first, according to RECIST 1.1 by BICR.
3. PFS, OR, and DOR according to RECIST 1.1 by Investigator.
4. DOR per RECIST 1.1 by Investigator (Dose Optimization).
5. PFS per RECIST 1.1 by Investigator and OS (Dose Optimization).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eikon Therapeutics Inc.

Sponsor organisation

Eikon Therapeutics Inc.

Address

450 East 29th Street Floor 15th

City

New York

Postcode

10016-8367

Country

United States

Scientific contact point

Organisation

Eikon Therapeutics Inc.

Contact name

Etah Kurland

Public contact point

Organisation

Eikon Therapeutics Inc.

Contact name

Krishna Kaza

Third parties 18

Locations

15 EU/EEA countries · 93 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 126 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications