EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial - 1)

NCT06923761 | Recruiting Phase 1

• 1 other identifier: GRWD5769-ST-01
• Study Type: interventional
• Target: 300
• Locations: 4 countries
• Sites: 29

Brief Summary

This is a Phase I/II, open-label, first-in human study of GRWD5769 alone, and in combination with another anti-cancer agent in advanced solid cancers.

Conditions

Advanced Solid Malignancy

Keywords

Oncology; ERAP 1; Solid tumors; TMB-H; NSCLC; Lung cancer; Cervical cancer; HCC - Hepatocellular Carcinoma; Liver cancer; Head and Neck Squamous Cell Carcinoma; SCCHN; Urothelial cancer; immuno oncology

Outcome Measures

Primary Outcomes (3)

• Number of treatment emergent and treatment related AEs

  Incidence of treatment emergent and treatment related AEs assessed from start of study drug to 30 days post last dose of GRWD5769 (Module 1) or to 90 days post last dose of cemiplimab (Module 2 Parts A-C).

  From first dose to 30 days after last dose of GRWD5769 for Module 1 and 90 days after last dose of cemiplimab for Module 2 Parts A-C.

• Incidence of Dose limiting toxicities (DLT)

  Incidence of Dose limiting toxicities (DLT) during the DLT period which commences Cycle 0 Day 1 and continues to 21 days after Cycle 1 Day 1

  End of cycle 1 (each cycle is 21 days)

• Comparative efficacy (for Module 2D only)

  Comparative efficacy will be evaluated or assessed using the change in dimension over time of RECIST Target Lesions from baseline and on-study scans recorded at weeks 8 and 16

  From baseline to week 16

Secondary Outcomes (17)

• GRWD5769 Plasma PK Trough concentration

  Up to approximately 1 year

• Objective response rate (ORR)

  Up to approximately 1 year

• Disease specific tumour markers

  Up to approximately 1 year

• GRWD5769 Plasma PK Cmax

  Up to approximately 1 year

• GRWD5769 Plasma PK Tmax

  Up to approximately 1 year

Study Arms (2)

Module 1 (GRWD5769 on its own as monotherapy)

EXPERIMENTAL

Drug: Module 1 (GRWD5769 on its own as monotherapy)

Module 2 (GRWD5769 in combination with cemiplimab, administered IV)

EXPERIMENTAL

Drug: Module 2 (GRWD5769 in combination with cemiplimab, administered IV)

Interventions

Module 1 (GRWD5769 on its own as monotherapy) DRUG

Module 1 will initially be conducted in 4 study parts: Part A: Monotherapy dose escalation (where the safety of increasing doses of GRWD5769 will initially be assessed in a small group of patients, overseen by a safety review committee) Part B: (Optional) Monotherapy dose expansion part (to look at the effect of GRWD5769 on the body, and of the body on GRWD5769, at particular dose levels to include evaluation of biopsies of tumour tissue) Part C: (Optional) Intra-patient dose escalation (where a patient may receive three different GRWD5769 doses so that blood levels at each dose can be measured in an individual) Part D: Monotherapy dose expansion group(s) (where a dose of GRWD5769 may be chosen to be evaluated in specific types of cancer)

Module 1 (GRWD5769 on its own as monotherapy)

Module 2 (GRWD5769 in combination with cemiplimab, administered IV) DRUG

Module 2 will initially be conducted as 3 study parts, similar to those above, but looking at GRWD5769 when given in combination with cemiplimab: Part A: Combination therapy dose escalation (like Module 1 Part A) Part B: (Optional) Combination therapy dose expansion part (like Module 1 Part B) Part C: Combination therapy dose expansion group(s) (where a dose of GRWD5769 given with cemiplimab will be evaluated in specific types of cancer) Part D: Randomised dose optimisation, combination therapy (where 3 doses of GRWD5769 given with cemiplimab will be evaluated in specific types of cancer)

Module 2 (GRWD5769 in combination with cemiplimab, administered IV)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent.
• Male or female, ≥ 18 years of age.
• An ECOG performance status of 0 or 1.
• Willing to permit access to stored historical tumour tissue and prior tumour radiological assessments and tumour biomarker data (if available).
• Able to take oral medications and be willing to record daily adherence to the study drug.
• Female participants must be of non-child-bearing potential, or, if of childbearing potential must have a negative pregnancy test (as required by protocol), must use a highly effective method of contraception combined with a condom and not donate ova (for the protocol specified period of time).
• Male participants must use a condom and their female participant must also use a highly effective method of contraception (for the protocol specified period of time), if engaging in sexual intercourse with a female partner who could become pregnant and not donate sperm.
• Estimated life expectancy of at least 3 months, in the opinion of the PI.
• Willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study procedures.
• Participant has measurable disease per RECIST 1.1/iRECIST
• Participant has cytologically or histologically confirmed locally advanced or metastatic solid malignancy for which no further standard of care (SoC) therapy is available (or no SoC therapy exists), or who have been offered and declined SoC therapy, or are intolerant of SoC therapy.
• Module 1 (Part B) and Module 2 (Part B) Only
• Participant has at least one tumour lesion amenable to serial biopsies and is willing to provide consent for biopsies and has measurable disease per RECIST 1.1/iRECIST, excluding the lesion(s) identified for biopsy.
• Module 2 (Part C and Part D)
• Cohort 1 (Cervical)

You may not qualify if:

• Prior therapy with an ERAP1 inhibitor.
• Any other malignancy within the past 3 years, with the exception of cervical intraepithelial neoplasia and nonmelanoma skin cancer.
• Any unresolved toxicity (except alopecia) from prior therapy of ≥ CTCAE Grade 1. Participants with Grade 2 toxicity that is not clinically significant (e.g., alopecia, vitiligo), or that is deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled.
• Active or documented history of autoimmune disease (within 2 years) requiring systemic immunosuppressive therapy, or participant is immunocompromised for any other reason (as determined by the Investigator).
• Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroids for at least 4 weeks (if stable and requiring no intervention, the participant can be enrolled in the study).
• Uncontrolled seizures.
• Active infection requiring therapy within 14 days prior to the day of first dose of IMP.
• Severe or uncontrolled medical condition (e.g., severe chronic obstructive pulmonary disease, severe Parkinson's disease, active inflammatory bowel disease) or psychiatric condition.
• Active bleeding diatheses.
• Participant has received an organ transplant.
• Known active hepatitis B, hepatitis C, or human immunodeficiency virus infection (HIV).
• Participant is breastfeeding or pregnant.
• Receipt of licenced or unlicenced cytotoxic, noncytotoxic or small molecule treatment for the malignancy within 28 days or 5 half-lives, whichever is shorter prior to the day of first dose of IMP.
• Receipt of oral corticosteroids (at a dose \> 10 mg prednisone/day or equivalent) within 14 days (except for subjects receiving corticosteroids for adrenal insufficiency).
• Receipt of St John's Wort or of another concomitant medication, herbal supplement, or food that is a strong inhibitor or inducer of CYP3A4 enzymes within 14 days.

Sponsors & Collaborators

• Grey Wolf Therapeutics: lead

Study Sites (29)

GenesisCare Research

Adelaide, Australia

WITHDRAWN

Southern Oncology Clinical Research Unit (SOCRU)

Bedford Park, Australia

RECRUITING

Blacktown Hospital

Blacktown, Australia

RECRUITING

Kinghorn Cancer Centre (KCC)

Darlinghurst, Australia

RECRUITING

Austin Health

Heidelberg, Australia

RECRUITING

Alfred Health

Melbourne, Australia

RECRUITING

Mater Research

South Brisbane, Australia

RECRUITING

Cancer Care Wollongong

Wollongong, Australia

RECRUITING

Centre Léon Bérard

Lyon, France

RECRUITING

Institut Paoli-Calmettes

Marseille, France

RECRUITING

Centre Eugène Marquis

Rennes, France

RECRUITING

Institut de Cancérologie de l'Ouest (ICO)

Saint-Herblain, France

RECRUITING

ICANS - Institut de Cancérologie Strasbourg

Strasbourg, France

RECRUITING

IUCT Oncopole - Institut Claudius Regaud

Toulouse, France

RECRUITING

Institut Gustave Roussy

Villejuif, France

RECRUITING

Hospital Universitario Vall d'Hebrón (VHIO)

Barcelona, Spain

RECRUITING

START Barcelona - Hospital HM Nou Delfos

Barcelona, Spain

RECRUITING

Clinica Universitaria de Navarra Madrid

Madrid, Spain

RECRUITING

START Madrid - Centro Integral Oncológico Clara Campal (HM CIOCC)

Madrid, Spain

RECRUITING

START Madrid - Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, Spain

RECRUITING

Clinica Universitaria de Navarra Pamplona

Pamplona, Spain

RECRUITING

INCLIVA-Hospital Clínico Universitario de Valencia

Valencia, Spain

RECRUITING

Western General Hospital

Edinburgh, United Kingdom

RECRUITING

Clatterbridge Cancer Centre

Liverpool, United Kingdom

RECRUITING

Hammersmith Hospitals NHS Trust

London, United Kingdom

RECRUITING

Royal Free Hospital

London, United Kingdom

RECRUITING

Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Newcastle Upon Tyne Hospital

Newcastle, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasms; Lung Neoplasms; Uterine Cervical Neoplasms; Carcinoma, Hepatocellular; Liver Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Central Study Contacts

Grey Wolf Therapeutics Patient enquiries

CONTACT

+44 1235644970; enquiries@gwt.bio

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2025
• First Posted: April 11, 2025
• Study Start: May 21, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: January 28, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8); GB (6); FR (7); AU (8)