A Pilot Study of Personalized Biomarker-based Treatment Strategy or Immunotherapy in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
Overview
- Phase
- Phase 2
- Intervention
- INCAGN01876
- Conditions
- Carcinoma, Squamous Cell of Head and Neck
- Sponsor
- European Organisation for Research and Treatment of Cancer - EORTC
- Enrollment
- 340
- Locations
- 33
- Primary Endpoint
- Progression Free Survival Rate (PFSR) at week 16
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a biomarker-driven trial that will enroll patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing after first-line platinum-based chemotherapy. Based on potential biomarkers and molecular alterations identified in the biopsy from the central platform, patients will be allocated in different cohorts. There will be biomarker-positive patient cohorts and immunotherapy cohorts.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed recurrent and/or metastatic SCCHN of the oral cavity, oropharynx, hypopharynx or larynx not amenable to curative treatment.
- •At least one measurable lesion by MRI or CT-scan according to RECIST 1.1, evaluated within 2 weeks prior to registration. Such lesion must not have been previously irradiated; if the measurable lesion(s) have been irradiated, clear progression must be documented.
- •Progressive disease after first line platinum-based chemotherapy with or without cetuximab given as palliative treatment or progressive disease within 1 year if platinum-based chemotherapy was given as a part of the multimodal curative treatment. Patients pre-treated with anti-PD1/anti-PDL1 are allowed.
- •ECOG performance status 0 -1 with a life expectancy of at least 12 weeks.
- •Tumor core biopsy from any accessible tumor at the recurrent or metastatic site available for central testing.
- •Patients must have adequate organ function, evaluated within 14 days prior to cohort allocation:
- •Hemoglobin ≥ 9 g/100 ml,
- •Neutrophils ≥ 1,500/mm3,
- •Platelets ≥ 100,000/mm3,
- •Total bilirubin \<1.5 times the upper limit of normal (ULN) (\< 3 times the upper limit of normal for Gilbert's disease),
Exclusion Criteria
- •Unresolved and significant toxicity CTCAE version 4.03 grade ≥ 2 from previous anticancer therapy other than alopecia.
- •History of any of the following cardiovascular conditions within 6 months prior to registration:
- •myocardial infarction,
- •severe/unstable angina,
- •ongoing cardiac dysrhythmias of CTCAE version 4.03 Grade 2 or more,
- •atrial fibrillation of any grade,
- •coronary/peripheral artery bypass graft,
- •symptomatic congestive heart failure according to New York Heart Association (NYHA) Class III or Class IV,
- •significant active cardiac disease including uncontrolled high blood pressure defined as systolic ≥150 and diastolic ≥
- •cerebrovascular accident including transient ischemic attack
Arms & Interventions
Patient Cohort I3
Patient who are progressing prior PD(L)1 after having received at least 2 months of anti-PD(L)-1 will receive INCAGN01876.
Intervention: INCAGN01876
Patient Cohort B1
Patients who are p16 negative and have an EGFR amplification/mutation or PTEN high or HER2 mutation/amplification will be randomized between afatinib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care).
Intervention: Afatinib
Patient Cohort B1
Patients who are p16 negative and have an EGFR amplification/mutation or PTEN high or HER2 mutation/amplification will be randomized between afatinib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care).
Intervention: standard of care
Patient Cohort B2
Patients who are p16 negative and cetuximab naïve will be randomized between afatinib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
Intervention: Afatinib
Patient Cohort B2
Patients who are p16 negative and cetuximab naïve will be randomized between afatinib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
Intervention: standard of care
Patient Cohort B3
Patients who are p16 negative and have an amplification of CCND1 will be randomized between palbociclib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
Intervention: Palbociclib
Patient Cohort B3
Patients who are p16 negative and have an amplification of CCND1 will be randomized between palbociclib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
Intervention: standard of care
Patient Cohort B4
Patients who are p16 negative and 'platinum sensitive' SCCHN will receive niraparib
Intervention: Niraparib
Patient Cohort B5
Patients whith oropharyngeal cancer and which are p16 positive will receive niraparib
Intervention: Niraparib
Patient Cohort I1
Patients who are anti-PD(L)1-naïeve or resistant (primary or secondary resistance) will receive IPH2201 antibody (monalizumab).
Intervention: IPH2201
Patient Cohort I2
Patient who are PD(L)1 pretreated will be randomized between monalizumab + durvalumab or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
Intervention: standard of care
Patient Cohort I2
Patient who are PD(L)1 pretreated will be randomized between monalizumab + durvalumab or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
Intervention: IPH2201
Patient Cohort I2
Patient who are PD(L)1 pretreated will be randomized between monalizumab + durvalumab or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
Intervention: Durvalumab
Outcomes
Primary Outcomes
Progression Free Survival Rate (PFSR) at week 16
Time Frame: The Progression Free Survival Rate (PFSR) analysis will be performed at week 16 for each patient in cohorts 1, 2 and 3.
Progression Free Survival Rate (PFSR) at week 16 will be assessed as primary endpoint for all patients from cohorts 1, 2 and 3.
Objective response Rate (ORR) at week 16
Time Frame: Objective response Rate (ORR) at week 16 will be performed at week 16 for each patient in cohort 4.
Objective response Rate (ORR) during the first 16 weeks of study treatment will be assessed as primary endpoint for all patients from cohort 4-8.
Secondary Outcomes
- Objective Response Rate(48 months after first patient in)
- The percentage of patients with an evaluable fresh tumor biopsy(42 months after first patient in)
- Percentage of patients included in each patient cohort according the biomarker testing(42 months after first patient in)
- Overall Survival (OS)(54 months after first patient in)
- Toxicity according CTCAE version 4.03(54 months after first patient in)
- Progression Free Survival (PFS)(54 months after first patient in)
- Response duration(54 months after first patient in)