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Trial record 1 of 1 for:    IO102-IO 103-032
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Phase II Trial of Neoadjuvant and Adjuvant IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Resectable Tumors

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ClinicalTrials.gov Identifier: NCT05280314
Recruitment Status : Recruiting
First Posted : March 15, 2022
Last Update Posted : February 21, 2024
Sponsor:
Collaborators:
Theradex
Almac
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
IO Biotech

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.

Condition or disease Intervention/treatment Phase
Melanoma Squamous Cell Carcinoma of Head and Neck Drug: IO102-IO103 Drug: Pembrolizumab KEYTRUDA® Phase 2

Detailed Description:

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. Approximately 30 patients with melanoma or SCCHN will be included (approximately 15 for each indication).During the neoadjuvant period, patients will receive IO102-IO103 and pembrolizumab KEYTRUDA® Q3W. Patients with melanoma will receive 3 doses of neoadjuvant treatment. Patients with SCCHN will receive 2 or 3 doses of neoadjuvant treatment, at the investigator's discretion. Surgical resection will be performed 1 to 3 weeks after the last dose of neoadjuvant treatment. All patients will receive post-surgery treatment with IO102-IO103 and pembrolizumab KEYTRUDA® for a total of 15 cycles (up to 45 weeks).

Patients with melanoma and patients with SCCHN who do not require SOC RT ± cisplatin will start post-surgery IO102-IO103 and pembrolizumab after adequate recovery from surgery (approximately 1 to 2 months; no more than 12 weeks).Patients with SCCHN who require postoperative SOC therapy after surgery will start post-surgery IO102-IO103 and pembrolizumab KEYTRUDA® after adequate recovery from SOC therapy (approximately 1 to 2 months; no more than 12 weeks).

Objective response will be based on imaging; pathologic tumor response of the surgical specimens will be assessed at the time of surgery. Safety will be assessed by recording adverse events. The primary endpoint will be the percentage of patients with major pathologic response (MPR) in the resected tumor tissue after neoadjuvant treatment. Secondary endpoints include disease-free survival (DFS) at 2 years after surgery. All patients will have an end-of-treatment visit approximately 4 weeks after their last dose of trial treatment. Follow-up visits will be conducted at 6 and 12 months after the end-of-treatment visit. Following completion of the 12-month follow-up period, long-term follow-up for overall survival (OS) will be conducted every 6 months for at least a further 12 month.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicenter, Multi-arm, Two indications, One Cohort per Indication
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II, Multi-cohort Trial of Neoadjuvant and Post-surgery IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Selected Resectable Tumors
Actual Study Start Date : December 21, 2023
Estimated Primary Completion Date : April 30, 2025
Estimated Study Completion Date : January 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

Drug: 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).

Drug: Pembrolizumab KEYTRUDA®
Pembrolizumab KEYTRUDA® administered intravenously

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.

Drug: 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).

Drug: Pembrolizumab KEYTRUDA®
Pembrolizumab KEYTRUDA® administered intravenously




Primary Outcome Measures :
  1. Major pathologic response [ Time Frame: Observed in the resected tumor tissue after neoadjuvant treatment at surgery ]
    Major pathologic response, defined as pathologic complete response (pCR) (0% residual viable tumor) or near pCR (≤10% residual viable tumor)


Secondary Outcome Measures :
  1. Pathologic complete response [ Time Frame: Observed in the resected tumor tissue after neoadjuvant treatment at surgery ]
    Pathologic complete response (pCR) (0% residual viable tumor)

  2. Pathologic tumor response [ Time Frame: Pathologic tumor response of the surgical specimens will be assessed at the time of surgery. ]
    Pathologic tumor response (≤ 49% residual viable tumor) at surgery

  3. Objective response rate [ Time Frame: Determined after 9 weeks of treatment ]
    Objective response rate (ORR), determined by RECIST 1.1

  4. Disease-free survival [ Time Frame: at 2 years after surgery ]
    Disease-free survival (DFS) from the date of surgery

  5. Event-free survival [ Time Frame: Determined after 9 weeks of treatment ]
    Event-free-survival (EFS)

  6. Event-free survival [ Time Frame: at 2 years after surgery ]
    Event-free-survival (EFS)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05280314


Contacts
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Contact: Diane McDowell SVP, Clinical Development and Medical Affairs, MD +1 267 252 7296 dmd@iobiotech.com
Contact: Shane O'Neill Clinical Program Director +44 790 433 7285 son@iobiotech.com

Locations
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United States, Connecticut
Yale Recruiting
New Haven, Connecticut, United States, 06519
Contact: Stacy Severin       stacy.severin@yale.edu   
Principal Investigator: Barbara Burtness         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Barry Anderson       banderson@theradex.com   
Contact: Kartik Sehgal       Kartik_Sehgal@DFCI.HARVARD.EDU   
Principal Investigator: Robert Haddad         
United States, Virginia
Massey Cancer Center Recruiting
Richmond, Virginia, United States, 23219
Contact: Carrie Donovan       cdonovan2@vcu.edu   
Principal Investigator: Erin Alesi, MD         
Australia, New South Wales
Melanoma Institute Australia The Uiniversity of Sydney, and Royal North Shore Hospital Recruiting
Sydney, New South Wales, Australia, Sydney 2060
Contact: Karen Bush       ealong@melanoma.org.au   
Principal Investigator: Georgina Long, MD         
Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3VIC 3000
Contact: Maria Vassiliou, Dr    (03)85595000    Maria.Vassiliou@petermac.org   
Contact: Caroline Suhr    (03)85595000    caroline.suhr@petermac.org <Caroline.Suhr@petermac.org>   
Principal Investigator: Annette Lim, Dr         
Sub-Investigator: Shahneen Sandhu, Dr         
Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark, 8200 Aarhus
Contact: Mona Kjaer       mona.kjaer@rm.dk   
Contact: Tina Kusk       tinakk@auh.rm.dk   
Principal Investigator: Rasmus Friis, Dr         
Copenhagen University Hospital Herlev Recruiting
Copenhagen, Denmark, 9 DK-2730
Contact: Signe Reinhold       signe.rud.reinhold@regionh.dk   
Principal Investigator: Inge Marie Svane, Dr         
France
CHRU Lille Recruiting
Lille, France, 59037 Lille
Contact: Sylvie Brice       sylvie.brice@chu-lille.fr   
Principal Investigator: Laurent Mortier, MD         
Hôpital Ambroise-Paré Recruiting
Paris, France, 92104 Boulogne
Contact: Veronique Clerisse       veronique.clerisse@aphp.fr   
Principal Investigator: Philippe Saiag, MD         
Institut Gustave Roussy Recruiting
Paris, France, 94805 Villejuif
Contact: Myriam Maalej-Chaari       myriam.maalej-chaari@gustaveroussy.fr   
Principal Investigator: Caroline Robert, MD         
Germany
Universitätsklinikum Essen & Research Alliance Ruhr Recruiting
Essen, Germany, D-45147 Essen
Contact: Katharina Metz       Katharina.Metz@uk-essen.de   
Principal Investigator: Dirk Schadendorf, MD         
Universität Heidelberg, Medizinische Fakultät Recruiting
Heidelberg, Germany, 69120 Heidelberg
Contact: Melanie Leieren       Melanie.Leierer@med.uni-heidelberg.de   
Principal Investigator: Jessica Hassell, MD         
Spain
Hospital Universitario Quirón Dexeus Recruiting
Barcelona, Spain, 08028 Barcelona
Contact: Carlos Esparre       Carlos Esparre <cesparre@oncorosell.com>   
Contact: Alba Silvestre       asilvestre@oncorosell.com   
Principal Investigator: Maria González Cao, Dr         
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain, Madrid 28034
Contact: Lucia Castillon       lcastillon@salud.madrid.org   
Contact: Pardo de Vera       bpardo@salud.madrid.org   
Principal Investigator: Aimaria Soria, Dr         
Hospital Clínico Universitario de Valencia -INCLIVA Recruiting
Valencia, Spain, 46010 Valencia
Contact: Inma Blasco       Inma Blasco <iblasco@incliva.es>   
Contact: Silvia Moreno       smoreno@incliva.es   
Principal Investigator: Ines González, Dr         
Sponsors and Collaborators
IO Biotech
Theradex
Almac
Merck Sharp & Dohme LLC
Investigators
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Principal Investigator: Barbara Burtness, MD, Prof Yale New Haven Hospital - Yale Cancer Center
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Responsible Party: IO Biotech
ClinicalTrials.gov Identifier: NCT05280314    
Other Study ID Numbers: IO102-IO103-032/IOB-032
MK-3475-E40 ( Other Identifier: Merck Sharp & Dohme LLC. )
First Posted: March 15, 2022    Key Record Dates
Last Update Posted: February 21, 2024
Last Verified: February 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Squamous Cell Carcinoma of Head and Neck
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Head and Neck Neoplasms
Neoplasms by Site
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action