Phase II Trial of Neoadjuvant and Adjuvant IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Resectable Tumors

NCT05280314 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IO102-IO103-032/IOB-032MK-3475-E40
• Study Type: interventional
• Target: 60
• Locations: 6 countries
• Sites: 15

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.

Conditions

Melanoma; Squamous Cell Carcinoma of Head and Neck

Outcome Measures

Primary Outcomes (1)

• Major pathologic response

  Major pathologic response, defined as pathologic complete response (pCR) (0% residual viable tumor) or near pCR (≤10% residual viable tumor)

  Observed in the resected tumor tissue after neoadjuvant treatment at surgery

Secondary Outcomes (6)

• Pathologic complete response

  Observed in the resected tumor tissue after neoadjuvant treatment at surgery

• Pathologic tumor response

  Pathologic tumor response of the surgical specimens will be assessed at the time of surgery.

• Objective response rate

  Determined after 9 weeks of treatment

• Disease-free survival

  at 2 years after surgery

• Event-free survival

  Determined after 9 weeks of treatment

Study Arms (3)

Cohort A - Melanoma

EXPERIMENTAL

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; Drug: Pembrolizumab KEYTRUDA®

Cohort B - SCCHN

EXPERIMENTAL

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; Drug: Pembrolizumab KEYTRUDA®

Cohort C

EXPERIMENTAL

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)

Drug: IO102-IO103; Drug: Pembrolizumab KEYTRUDA®

Interventions

IO102-IO103 DRUG

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).

Cohort A - Melanoma; Cohort B - SCCHN; Cohort C

Pembrolizumab KEYTRUDA® DRUG

Pembrolizumab KEYTRUDA® administered intravenously

Cohort A - Melanoma; Cohort B - SCCHN; Cohort C

Eligibility Criteria

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

You may qualify if:

• 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
• 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.
• Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
• Candidate for surgical resection with curative intent
• The patient (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Age ≥18 years on the day of signing the informed consent form
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance score status of 0 or 1
• Adequate organ function as defined below performed on screening labs obtained within 4 weeks before first dose:

You may not qualify if:

• 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
• Nasopharyngeal cancer, unknown primary, nasal cavity or paranasal sinus carcinoma
• In addition, patients meeting any of the following criteria must be excluded:
• 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.
• Any prior treatment for the tumor under study
• 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)
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• IO Biotech: lead
• Theradex: collaborator
• Almac: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (15)

Yale

New Haven, Connecticut, 06519, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Massey Cancer Center

Richmond, Virginia, 23219, United States

RECRUITING

Melanoma Institute Australia The Uiniversity of Sydney, and Royal North Shore Hospital

Sydney, New South Wales, Sydney 2060, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3VIC 3000, Australia

RECRUITING

Aarhus University Hospital

Aarhus, 8200 Aarhus, Denmark

RECRUITING

Copenhagen University Hospital Herlev

Copenhagen, 9 DK-2730, Denmark

RECRUITING

CHRU Lille

Lille, 59037 Lille, France

RECRUITING

Hôpital Ambroise-Paré

Paris, 92104 Boulogne, France

RECRUITING

Institut Gustave Roussy

Paris, 94805 Villejuif, France

RECRUITING

Universitätsklinikum Essen & Research Alliance Ruhr

Essen, D-45147 Essen, Germany

RECRUITING

Universität Heidelberg, Medizinische Fakultät

Heidelberg, 69120 Heidelberg, Germany

RECRUITING

Hospital Universitario Quirón Dexeus

Barcelona, 08028 Barcelona, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, Madrid 28034, Spain

RECRUITING

Hospital Clínico Universitario de Valencia -INCLIVA

Valencia, 46010 Valencia, Spain

RECRUITING

MeSH Terms

Conditions

Melanoma; Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms

Study Officials

• Barbara Burtness, MD, Prof

  Yale New Haven Hospital - Yale Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diane McDowell SVP, Clinical Development and Medical Affairs, MD

CONTACT

+1 267 252 7296; dmd@iobiotech.com

Shane O'Neill Clinical Program Director

CONTACT

+44 790 433 7285; son@iobiotech.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, Multi-arm, Two indications, One Cohort SCCHN 2 Cohorts melanoma (1 cohort randomized and one cohort not randomized)

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: March 15, 2022
• Study Start: December 21, 2023
• Primary Completion: April 30, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 18, 2024

Record last verified: 2024-03

Locations

DE (2); DK (2); US (3); AU (2); FR (3); ES (3)