Phase II, multi-cohort trial of neoadjuvant and post-surgery IO102-IO103 and pembrolizumab in patients with selected resectable tumors
- Conditions
- Melanoma and squamous cell carcinoma of the head and neckMedDRA version: 20.0Level: LLTClassification code: 10040891Term: Skin melanoma Class: 10029104MedDRA version: 21.0Level: PTClassification code: 10060121Term: Squamous cell carcinoma of head and neck Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2022-502787-20-00
- Lead Sponsor
- IO Biotech ApS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 90
Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, HIV-infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as: aPatients on ART must have a CD4+ T-cell count ?350 cells/mm3 at time of screening bPatients 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) cPatients 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), 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, Patients with a history of hepatitis C (HCV) infection are eligible if HCV viral load is undetectable at screening, 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: oPrimary cutaneous melanoma with clinically apparent regional lymph node metastases oClinically detected recurrent melanoma at the proximal regional lymph node(s) basin oClinically detected primary cutaneous melanoma involving multiple regional nodal groups oClinically detected nodal melanoma (if single site) arising from an unknown primary oRelapsed resectable stage III melanoma, SCCHN-specific inclusion criteria: • Newly diagnosed and histologically confirmed SCCHN that presents as locoregionally advanced (stage III or IVA) resectable disease of the oral cavity, oropharynx (with known HPV-negative or p16-negative status assessed per institution standard), hypopharynx, or larynx, 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 (=3 months old) or newly obtained core or excisional biopsy of a tumor lesion (primary tumor and/or lymph node) not previously irradiated., Eastern Cooperative Oncology Group (ECOG) performance score status of 0 or 1, Adequate organ function, Women of childbearing potential: Negative urine or serum pregnancy within 72 hours prior to receiving the first dose of trial medication., 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
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, History of radiation pneumonitis, History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, Active infection requiring systemic therapy, HIV-infected patients with a history of Kaposi sarcoma and/or Multicentric Castleman Disease, Has known active hepatitis B virus or known active hepatitis C virus (HCV) infection, 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, Psychiatric or substance abuse disorders that would interfere with the patient’s ability to cooperate with the trial requirements, Severe hypersensitivity (grade =3) to pembrolizumab and/or any of its excipients, Women of childbearing potential: Pregnant or breastfeeding, or expecting to conceive a child within the projected duration of the trial, from time of informed consent until at least 120 days after the last dose of trial treatment, Melanoma-specific exclusion criteria: •Current or prior history of uveal, mucosal, or acral melanoma • Oligometastatic stage IV melanoma • History of in-transit or satellite metastases within the last 6 months •Prior therapy targeting BRAF and/or MEK, Any prior systemic treatment for the tumor under study. Melanoma patients may have received prior non-immunotherapy adjuvant therapy if more than 6 months prior to the first dose of trial treatment., SCCHN-specific exclusion criteria: •Nasopharyngeal cancer, unknown primary, nasal cavity or paranasal sinus carcinoma, Prior therapy 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., Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of trial treatment, Live or live-attenuated vaccine within 30 days prior to the first dose of trial treatment, 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, History of an allogeneic tissue/solid organ transplant, Active autoimmune disease that has required systemic treatment in past 2 years. Patients with type I diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders not requiring systemic treatment; or conditions not expected to recur in the absence of an external trigger are permitted to enroll
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate the efficacy of neoadjuvant treatment with IO102-IO103 in combination with pembrolizumab, in terms of major pathological response (MPR) in resected tumors.;Secondary Objective: •To investigate the efficacy of IO102-IO103 in combination with pembrolizumab as neoadjuvant treatment in terms of pathological complete response (pCR), pathological response rate and objective response rate (ORR), • To investigate the efficacy of IO102-IO103 in combination with pembrolizumab as neoadjuvant and post-surgery treatment in terms of event-free survival (EFS) and disease-free survival (DFS), •To investigate the safety and tolerability of IO102-IO103 in combination with pembrolizumab as neoadjuvant and post-surgery treatment;Primary end point(s): MPR, defined as pCR (0% residual viable tumor) or near pCR (=10% residual viable tumor) at surgery (central assessment)
- Secondary Outcome Measures
Name Time Method Secondary end point(s):pCR (0% residual viable tumor) at surgery (central assessment);Secondary end point(s):Pathological response rate (% of patients with pPR, near pCR or pCR) (central assessment);Secondary end point(s):ORR, determined by RECIST 1.1, at the end of neoadjuvant treatment (investigator assessment);Secondary end point(s):EFS from the start of neoadjuvant treatment (investigator assessment);Secondary end point(s):DFS from the date of surgery (investigator assessment);Secondary end point(s):Safety endpoints • Incidence of adverse events (AEs) • Incidence of serious adverse events (SAEs) • Incidence of treatment-related AEs • Incidence of treatment-related SAEs • Incidence of AEs leading to discontinuation of trial treatment