Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06923761




Registration number
NCT06923761
Ethics application status
Date submitted
27/03/2025
Date registered
11/04/2025
Date last updated
19/06/2025

Titles & IDs
Public title
EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial - 1)
Scientific title
A Modular, Multi-part, Multi-arm, Open-label, Phase I/II Study to Evaluate the Safety and Tolerability of GRWD5769 Alone and in Combination With Anticancer Treatments in Patients With Solid Malignancies
Secondary ID [1] 0 0
GRWD5769-ST-01
Universal Trial Number (UTN)
Trial acronym
EMITT-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Malignancy 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Module 1 (GRWD5769 on its own as monotherapy)
Treatment: Drugs - Module 2 (GRWD5769 in combination with cemiplimab, administered IV)

Experimental: Module 1 (GRWD5769 on its own as monotherapy) -

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


Treatment: Drugs: Module 1 (GRWD5769 on its own as monotherapy)
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)

Treatment: Drugs: Module 2 (GRWD5769 in combination with cemiplimab, administered IV)
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)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of treatment emergent and treatment related AEs
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
Incidence of Dose limiting toxicities (DLT)
Timepoint [2] 0 0
End of cycle 1 (each cycle is 21 days)
Secondary outcome [1] 0 0
GRWD5769 Plasma PK Trough concentration
Timepoint [1] 0 0
Up to approximately 1 year
Secondary outcome [2] 0 0
Objective response rate (ORR)
Timepoint [2] 0 0
Up to approximately 1 year
Secondary outcome [3] 0 0
Disease specific tumour markers
Timepoint [3] 0 0
Up to approximately 1 year
Secondary outcome [4] 0 0
GRWD5769 Plasma PK Cmax
Timepoint [4] 0 0
Up to approximately 1 year
Secondary outcome [5] 0 0
GRWD5769 Plasma PK Tmax
Timepoint [5] 0 0
Up to approximately 1 year
Secondary outcome [6] 0 0
GRWD5769 Plasma PK AUC0-t
Timepoint [6] 0 0
Up to approximately 1 year
Secondary outcome [7] 0 0
GRWD5769 Plasma PK Half-life
Timepoint [7] 0 0
Up to approximately 1 year
Secondary outcome [8] 0 0
GRWD5769 Plasma PK Oral Clearance
Timepoint [8] 0 0
Up to approximately 1 year
Secondary outcome [9] 0 0
GRWD5769 Plasma PK Vss/F
Timepoint [9] 0 0
Up to approximately 1 year
Secondary outcome [10] 0 0
Disease Control Rate (DCR)
Timepoint [10] 0 0
Up to approximately 1 year
Secondary outcome [11] 0 0
Stable Disease Rate (SDR)
Timepoint [11] 0 0
Up to approximately 1 year
Secondary outcome [12] 0 0
Time To Response (TTR)
Timepoint [12] 0 0
Up to approximately 1 year
Secondary outcome [13] 0 0
Duration Of Response (DOR)
Timepoint [13] 0 0
Up to approximately 1 year
Secondary outcome [14] 0 0
Progression - Free Survival (PFS)
Timepoint [14] 0 0
Up to approximately 1 year

Eligibility
Key inclusion criteria
1. Provision of written informed consent.
2. Male or female, = 18 years of age.
3. An ECOG performance status of 0 or 1.
4. Willing to permit access to stored historical tumour tissue and prior tumour radiological assessments and tumour biomarker data (if available).
5. Able to take oral medications and be willing to record daily adherence to the study drug.
6. 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).
7. 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.
8. Estimated life expectancy of at least 3 months, in the opinion of the PI.
9. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study procedures.

Module 1 (Parts A, B and C) and Module 2 (Parts A and B)
10. 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 (Parts A, B and C) and Module 2 (Parts A and B) only
11. Participant has measurable disease per RECIST 1.1/iRECIST.

Module 1 (Part B) and Module 2 (Part B) Only
12. 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) Cohort 1
13. Participants with histologically confirmed persistent, recurrent or metastatic cervical cancer who are not amenable to curative therapy.
14. Participants should have received at least 3 months first line anti-PD(L)-1 maintenance therapy (± bevacizumab) following combination with chemotherapy + anti-PD-(L)1 ± bevacizumab and this should have included at least a 10-week period without progression.
15. Participants may enrol in the study immediately following progression on the first line CPI or may have received 1 further line of systemic cancer therapy after progression on CPI.

Cohort 2
16. Participants with histologically confirmed hepatocellular carcinoma who are not amenable to curative therapy and ineligible for loco-regional therapy.
17. Participants should have received at least 3 months first line anti-PD(L)-1 containing therapy and this should have included at least a 10-week period without progression per Investigator assessment.
18. Participants may enrol in the study immediately following progression on the first line CPI or may have received 1 further line of systemic cancer therapy after progression on CPI.
19. Participant has Child-Pugh score class A liver function.

Cohort 3
20. Participants with cytologically or histologically confirmed advanced, recurrent or metastatic disease, which is not amenable to curative therapy, in up to 5 types of solid tumour with moderate to high median TMB (NSCLC, urothelial, SCCHN, gastric/gastro-oesophageal adenocarcinoma, oesophageal SCC).
21. Participants should have received at least = 3 months first line anti-PD(L)-1 either initiated as monotherapy or following completion of chemotherapy + anti PD-(L)1.
22. Participants may enrol in the study immediately following progression on the first line CPI or may have received 1 further line of systemic cancer therapy after progression on CPI.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior therapy with an ERAP1 inhibitor.
2. Any other malignancy within the past 3 years, with the exception of cervical intraepithelial neoplasia and nonmelanoma skin cancer.
3. 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.
4. 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).
5. 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).
6. Uncontrolled seizures.
7. Active infection requiring therapy within 14 days prior to the day of first dose of IMP.
8. Severe or uncontrolled medical condition (e.g., severe chronic obstructive pulmonary disease, severe Parkinson's disease, active inflammatory bowel disease) or psychiatric condition.
9. Active bleeding diatheses.
10. Participant has received an organ transplant.
11. Known active hepatitis B, hepatitis C, or human immunodeficiency virus infection (HIV).
12. Participant is breastfeeding or pregnant.
13. 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.
14. Receipt of oral corticosteroids (at a dose > 10 mg prednisone/day or equivalent) within 14 days (except for subjects receiving corticosteroids for adrenal insufficiency).
15. 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.
16. Receipt of a blood transfusion (blood or blood products) within 7 days.
17. Impaired hepatic or renal function.
18. Liver function deteriorating in a manner that would likely make the participant ineligible per protocol specified requirements.
19. Other evidence of impaired hepatic synthesis function.
20. Inadequate bone marrow reserve or organ function.
21. Any prior history of persistent (> 4 weeks) severe pancytopenia due to previous therapy rather than to disease (ANC < 0.5 × 10^9/L or platelets < 50 x 10^9/L).
22. Cardiac dysfunction or other clinically significant cardiac pathology likely to impair the participants ability to participate in the study.
23. Mean QTcF > 450 ms for males or > 470 ms for females.
24. Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG. Controlled atrial fibrillation is permitted.
25. Any factor that in the Investigator's opinion increases the risk of QTc prolongation or arrythmic events.
26. In the opinion of the Investigator, unlikely to comply with study procedures, restrictions, or requirements.
27. A history of haemolytic anaemia or marrow aplasia.
28. Has received a live-virus vaccination within 28 days. Note: seasonal flu or COVID vaccines that do not contain live virus are permitted.
29. History of Grade 3 or 4 pneumonitis or interstitial lung disease within the last 5 years, or other clinically significant pulmonary pathology likely to impair ability to participate in the study.

Module 2 all Parts and Module 1A Crossover Participants Only Only
30. Has discontinued a prior checkpoint inhibitor due to toxicity.
31. Hypersensitivity to cemiplimab or any of its excipients, or contraindicated to cemiplimab per approved local labelling.
32. Has experienced = Grade 2 immune-mediated AE on this study (applies to crossover participants only).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/05/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2028
Actual
Sample size
Target
288
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
GenesisCare Research - Adelaide
Recruitment hospital [2] 0 0
Southern Oncology Clinical Research Unit (SOCRU) - Bedford Park
Recruitment hospital [3] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [4] 0 0
Kinghorn Cancer Centre (KCC) - Darlinghurst
Recruitment hospital [5] 0 0
Austin Health - Heidelberg
Recruitment hospital [6] 0 0
Alfred Health - Melbourne
Recruitment hospital [7] 0 0
Mater Research - South Brisbane
Recruitment hospital [8] 0 0
Cancer Care Wollongong - Wollongong
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Bedford Park
Recruitment postcode(s) [3] 0 0
- Blacktown
Recruitment postcode(s) [4] 0 0
- Darlinghurst
Recruitment postcode(s) [5] 0 0
- Heidelberg
Recruitment postcode(s) [6] 0 0
- Melbourne
Recruitment postcode(s) [7] 0 0
- South Brisbane
Recruitment postcode(s) [8] 0 0
- Wollongong
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Lyon Cedex
Country [2] 0 0
France
State/province [2] 0 0
Marseille
Country [3] 0 0
France
State/province [3] 0 0
Rennes
Country [4] 0 0
France
State/province [4] 0 0
Saint-Herblain Cedex
Country [5] 0 0
France
State/province [5] 0 0
Strasbourg
Country [6] 0 0
France
State/province [6] 0 0
Toulouse
Country [7] 0 0
France
State/province [7] 0 0
Villejuif
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Madrid
Country [10] 0 0
Spain
State/province [10] 0 0
Malaga
Country [11] 0 0
Spain
State/province [11] 0 0
Pamplona
Country [12] 0 0
Spain
State/province [12] 0 0
Valencia
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Edinburgh
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Liverpool
Country [15] 0 0
United Kingdom
State/province [15] 0 0
London
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Manchester
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Newcastle

Funding & Sponsors
Primary sponsor type
Other
Name
Grey Wolf Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Grey Wolf Therapeutics Patient enquiries
Address 0 0
Country 0 0
Phone 0 0
+44 1235644970
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD may not be shared for this Phase 1 study, or the IPD plan may be updated at a later point.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06923761