Melanoma, Squamous Cell Carcinoma of Head and Neck
Conditions
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.
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 60 patients with melanoma or SCCHN will be included (approximately 15 for each indication).During the neoadjuvant period, patients in cohort A, cohort B and Cohort C (Arm A) will receive IO102-IO103 and pembrolizumab KEYTRUDA® Q3W. Patients in Cohort C (Arm B) will receive pembrolizumab KEYTRUDA® 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 in cohort A,B and Cohort C (Arm A)will receive post-surgery treatment with IO102-IO103 and pembrolizumab KEYTRUDA® for a total of 15 cycles (up to 45 weeks). Patients in Cohort C (Arm B) will receive post-surgery treatment with 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 treatment 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.
Interventions
DRUGIO102-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).
Pembrolizumab KEYTRUDA® administered intravenously
Sponsors
Theradex
Almac
Merck Sharp & Dohme LLC
IO Biotech
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicenter, Multi-arm, Two indications, One Cohort SCCHN 2 Cohorts melanoma (1 cohort randomized and one cohort not randomized)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major pathologic response | 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
| Measure | Time frame | Description |
|---|---|---|
| Pathologic complete response | Observed in the resected tumor tissue after neoadjuvant treatment at surgery | Pathologic complete response (pCR) (0% residual viable tumor) |
| Pathologic tumor response | Pathologic tumor response of the surgical specimens will be assessed at the time of surgery. | Pathologic tumor response (≤ 49% residual viable tumor) at surgery |
| Objective response rate | Determined after 9 weeks of treatment | Objective response rate (ORR), determined by RECIST 1.1 |
| Disease-free survival | at 2 years after surgery | Disease-free survival (DFS) from the date of surgery |
| Event-free survival | Determined after 9 weeks of treatment | Event-free-survival (EFS) |
Countries
Australia, Denmark, France, Germany, Spain, United States
Contacts
Primary ContactDiane McDowell SVP, Clinical Development and Medical Affairs, MD
Backup ContactShane O'Neill Clinical Program Director
Outcome results
None listed