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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05280314




Registration number
NCT05280314
Ethics application status
Date submitted
22/02/2022
Date registered
15/03/2022
Date last updated
18/03/2024

Titles & IDs
Public title
Phase II Trial of Neoadjuvant and Adjuvant IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Resectable Tumors
Scientific title
Phase II, Multi-cohort Trial of Neoadjuvant and Post-surgery IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Selected Resectable Tumors
Secondary ID [1] 0 0
MK-3475-E40
Secondary ID [2] 0 0
IO102-IO103-032/IOB-032
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Squamous Cell Carcinoma of Head and Neck 0 0
Condition category
Condition code
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IO102-IO103
Treatment: Drugs - Pembrolizumab KEYTRUDA®

Experimental: Cohort A - Melanoma - Cutaneous resectable Stage III melanoma.

Neoadjuvant Treatment (3 cycles): Subcutaneous IO102-IO103 (IO102 85 µg and IO103 85 µg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W.

Post-surgery Treatment (15 cycles): Subcutaneous IO102-IO103 (IO102 85 µg and IO103 85 µg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W.

Experimental: Cohort B - SCCHN - Stage III or IVA resectable locoregionally advanced Squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx (HPV-negative), hypopharynx, or larynx

Neoadjuvant Treatment (2-3 cycles): Subcutaneous IO102-IO103 (IO102 85 µg and IO103 85 µg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W Post-surgery Treatment (15 cycles): Subcutaneous IO102-IO103 (IO102 85 µg and IO103 85 µg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W.

Experimental: Cohort C - Cutaneous resectable Stage III melanoma. Neoadjuvant Treatment (3 cycles): Subcutaneous IO102-IO103 (IO102 85 µg and IO103 85 µg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W (Arm A) versus intravenous Pembrolizumab KEYTRUDA® 200mg Q3W alone (Arm B) Post-surgery Treatment (15 cycles): Subcutaneous IO102-IO103 (IO102 85 µg and IO103 85 µg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W (Arm A) versus Pembrolizumab KEYTRUDA® 200mg Q3W alone (Arm B)


Treatment: Drugs: IO102-IO103
IO102-IO103 is a combination of an indoleamine 2,3-dioxygenase 1 (IDO1) peptide (IO102) and a programmed death-ligand 1 (PD-L1) peptide (IO103), emulsified with an adjuvant (Montanide ISA 51 VG).

Treatment: Drugs: Pembrolizumab KEYTRUDA®
Pembrolizumab KEYTRUDA® administered intravenously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Major pathologic response
Timepoint [1] 0 0
Observed in the resected tumor tissue after neoadjuvant treatment at surgery
Secondary outcome [1] 0 0
Pathologic complete response
Timepoint [1] 0 0
Observed in the resected tumor tissue after neoadjuvant treatment at surgery
Secondary outcome [2] 0 0
Pathologic tumor response
Timepoint [2] 0 0
Pathologic tumor response of the surgical specimens will be assessed at the time of surgery.
Secondary outcome [3] 0 0
Objective response rate
Timepoint [3] 0 0
Determined after 9 weeks of treatment
Secondary outcome [4] 0 0
Disease-free survival
Timepoint [4] 0 0
at 2 years after surgery
Secondary outcome [5] 0 0
Event-free survival
Timepoint [5] 0 0
Determined after 9 weeks of treatment
Secondary outcome [6] 0 0
Event-free survival
Timepoint [6] 0 0
at 2 years after surgery

Eligibility
Key inclusion criteria
Melanoma-specific inclusion criteria:

• Histologically or cytologically confirmed diagnosis of cutaneous stage III melanoma according to the American Joint Committee on Cancer (AJCC) 8th edition.

Patients with resectable tumors are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal metastasis or at the time of clinically detected nodal recurrence; they may belong to any of the following groups:

* Primary cutaneous melanoma with clinically apparent regional lymph node metastases
* Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin
* Clinically detected primary cutaneous melanoma involving multiple regional nodal groups
* Clinically detected nodal melanoma (if single site) arising from an unknown primary
* Relapsed resectable stage III melanoma

SCCHN-specific inclusion criteria:

• Stage III or IVA resectable locoregionally advanced SCCHN of the oral cavity, oropharynx (with known HPV-negative or p16-negative status assessed per institution standard or centrally), hypopharynx, or larynx.

Inclusion criteria applicable across cohorts:

In addition to the indication-specific inclusion criteria, a patient must meet all the following general criteria to be eligible for participation in this trial:

1. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
2. Candidate for surgical resection with curative intent
3. The patient (or legally acceptable representative if applicable) provides written informed consent for the trial.
4. Age =18 years on the day of signing the informed consent form
5. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
6. Eastern Cooperative Oncology Group (ECOG) performance score status of 0 or 1
7. Adequate organ function as defined below performed on screening labs obtained within 4 weeks before first dose:

* Absolute neutrophil count (ANC) =1500/µL
* Platelets =100 000/µL
* Hemoglobin =9.0 g/dL or =5.6 mmol/L (Note: Criterion must be met without packed red blood cell transfusion within the prior 2 weeks. Patients can be on stable dose of erythropoietin [= approximately 3 months].)
* Creatinine or measured or calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance) =1.5 × upper limit of normal (ULN) or =30 mL/min for patient with creatinine levels >1.5 × institutional ULN
* Serum total bilirubin =1.5 × ULN or direct bilirubin = ULN for patients with total bilirubin levels >1.5 × ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × ULN
* International normalized ratio (INR) or prothrombin time (PT) =1.5 × ULN unless the patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within the therapeutic range of intended use of anticoagulants
* Activated partial thromboplastin time (aPTT) =1.5 × ULN unless the patient is receiving anticoagulant therapy as long as PT or PTT is within the therapeutic range of intended use of anticoagulants
8. Women of childbearing potential: Negative urine or serum pregnancy within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
9. Women of childbearing potential: Willing to use highly effective contraception or abstain from heterosexual activity for the duration of the trial and for at least 120 days after the last dose of trial medication
10. HIV-infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:

a Patients on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening b Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to first dose of trial medication (Day 1) c Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to first dose of trial medication (Day 1) 11. Patients who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to start of trial intervention.

Note: Patients should remain on anti-viral therapy throughout trial intervention and follow local guidelines for HBV anti-viral therapy after completion of trial intervention.

Hepatitis B screening tests are not required unless:

* Known history of HBV infection
* Mandated by local health authority. 12. Patients with a history of hepatitis C (HCV) infection are eligible if HCV viral load is undetectable at screening.

Note: Patients must have completed curative antiviral therapy at least 4 weeks prior to start of trial intervention.

Hepatitis C screening tests are not required unless:

* Known history of HCV infection
* Mandated by local health authority.

Melanoma-specific exclusion criteria:

* Current or prior history of uveal, mucosal, or acral melanoma
* Oligometastatic stage IV melanoma
* History of in-transit metastases within the last 6 months
* Prior therapy targeting BRAF and/or MEK

SCCHN-specific exclusion criteria:

• Nasopharyngeal cancer, unknown primary, nasal cavity or paranasal sinus carcinoma
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria applicable across cohorts:

In addition, patients meeting any of the following criteria must be excluded:

1. Currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks of the first dose of trial treatment Note: Patients who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
2. Any prior treatment for the tumor under study
3. Prior therapy for another tumor with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137), and discontinued from that treatment due to a grade 3 or higher immune-related adverse event (irAE)
4. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of trial treatment

* Note: Patients must have recovered from all adverse events (AEs) due to previous therapies (i.e., grade =1 at baseline). Patients with grade =2 neuropathy are eligible for the trial. Patients with endocrine-related AEs grade =2 requiring treatment or hormone replacement are also eligible.
* Note: If the patient has had major surgery, the patient must have recovered adequately from the procedure and/or complications from the surgery prior to starting trial treatment.
5. Live or live-attenuated vaccine within 30 days prior to the first dose of trial treatment. Note: Administration of inactivated vaccines, mRNA-based vaccines [e.g., COVID-19] and vector-based vaccines are allowed.
6. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients who are currently receiving steroids at a dose equivalent to <5 mg/day of prednisone do not need to discontinue steroids prior to enrollment. Patients who require topical, ophthalmologic and inhalational steroids will not be excluded from the trial. Patients with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the trial.
7. Additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
8. History of an allogeneic tissue/solid organ transplant.
9. Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Patients with type I diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment; or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
10. History of radiation pneumonitis
11. History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
12. Active infection requiring systemic therapy
13. HIV-infected patients with a history of Kaposi sarcoma and/or Multicentric Castleman Disease
14. Has known active hepatitis B virus (HBV; defined as hepatitis B surface antigen [HBsAg] reactive and/or detectable HBV DNA) or known active hepatitis C virus (HCV) (defined as anti HCV Ab positive and detectable HCV ribonucleic acid [RNA] [qualitative]) infection.

Note: Testing for hepatitis B and hepatitis C is not required unless
1. Known history of HBV or HCV infection
2. Mandated by local health authority. Patients with a history of hepatitis will be screened using serology to confirm status.
15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
16. Psychiatric or substance abuse disorders that would interfere with the patient's ability to cooperate with the trial requirements
17. Severe hypersensitivity (grade =3) to pembrolizumab and/or any of its excipients

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
Parallel
Other design features
Phase
Phase 2
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
21/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2027
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Melanoma Institute Australia The Uiniversity of Sydney, and Royal North Shore Hospital - Sydney
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
Sydney 2060 - Sydney
Recruitment postcode(s) [2] 0 0
3VIC 3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Virginia
Country [4] 0 0
Denmark
State/province [4] 0 0
Aarhus
Country [5] 0 0
Denmark
State/province [5] 0 0
Copenhagen
Country [6] 0 0
France
State/province [6] 0 0
Lille
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
Germany
State/province [8] 0 0
Essen
Country [9] 0 0
Germany
State/province [9] 0 0
Heidelberg
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona
Country [11] 0 0
Spain
State/province [11] 0 0
Madrid
Country [12] 0 0
Spain
State/province [12] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
IO Biotech
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Theradex
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Almac
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Merck Sharp & Dohme LLC
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, multi-arm trial evaluating anti-tumor activity, safety, and immune infiltration of IO102-IO103 in combination with pembrolizumab KEYTRUDA® as neoadjuvant and post-surgery treatment. This proof-of-concept trial will include patients with resectable tumors in at least 2 indications.
Trial website
https://clinicaltrials.gov/study/NCT05280314
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Barbara Burtness, MD, Prof
Address 0 0
Yale New Haven Hospital - Yale Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Diane McDowell SVP, Clinical Development and Medical Affairs, MD
Address 0 0
Country 0 0
Phone 0 0
+1 267 252 7296
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05280314