Non-Small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10029518 Term: Non-small cell lung cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10029519 Term: Non-small cell lung cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10029520 Term: N
Conditions
Interventions
Product Code: IPH5201
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: not assigned yet
CAS Number: N/A
Current Sponsor code: HUB3-M-HNT392-10D10-H4L1
Other d
Sponsors
Innate Pharma SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol. 2.Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling, and analyses – including collection of samples for genetic analysis, if applicable. 3.Patients must be = 18 years at the time of screening. 4.Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC. Patients should have resectable (Stage IIA to Stage IIIA) disease (according to Version 8 of IASLC Staging Manual in Thoracic Oncology 2016. For patients with N2 disease, only those with 1 single nodal station = 3 cm are eligible) and be candidate for lobectomy, sleeve resection, or bilobectomy at the time of screening. 5. WHO PS or ECOG PS of 0 or 1 at enrolment. 6. Adequate organ and marrow function as defined below: • Haemoglobin = 9.0 g/dL. • Absolute neutrophil count (ANC) = 1.5 × 109/L. • Platelet count = 100 × 109/L. • Serum bilirubin = 1.5 × Upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician. • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN. • Measured creatinine clearance (CrCL) > 40 mL/min or calculated CrCL > 40 mL/min as determined by Cockcroft-Gault formula using actual body weight (Cockroft and Gault, 1976) (https://www.kidney.org/professionals/KDOQI/gfr_calculatorCoc). 7. Must have a life expectancy of at least 12 weeks. 8. Body Weight > 35 kg. 9. Male and/or female. 10. Negative pregnancy test (serum or urine) for women of childbearing potential. 11. Provision of tumor samples (newly acquired [preferred] or archival tumor tissue [= 6 months old]) to confirm PD-L1 status, EGFR, or ALK status where required during screening and prior to nC1D1. Provision of tumor samples appropriate for exploratory biomarker analyses. 13. Patients will be suitable for inclusion if the planned surgery to be performed will be lobectomy, sleeve resection, or bilobectomy, as determined by the attending surgeon based on the baseline findings. Patients whose planned surgery at enrolment includes pneumonectomy, segmentectomies, or wedge resections are not eligible for this study. 14. A pre- or post-bronchodilator FEV1 of 1.0 L and DLCO > 40% postoperative predicted value. Use of these cut-off values to assess candidacy for resection should be guided by the results of cardiopulmonary exercise testing as outlined in the ESMO guidelines on pre-treatment risk assessment. Both an FEV1 and a DLCO test are required for assessing lung function at screening. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: 1.Patients with sensitizing EGFR mutations or ALK translocations. 2.History of allogeneic organ transplantation. 3.Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [e.g., granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, or uveitis]). The following are exceptions to this criterion: • Patients with vitiligo or alopecia. • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. • Any chronic skin condition that does not require systemic therapy. Page 12/101 • Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician/Medical Scientist. • Patients with celiac disease controlled by diet alone. 4. Uncontrolled intercurrent illness, including but not limited to, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent. 5. History of any grade of venous or arterial thromboembolic events including cerebrovascular accident, transient ischemic attack, or unstable angina pectoris within 6 months prior to enrollment. 6. History of another primary malignancy, except for the following: • Malignancy treated with curative intent and with no known active disease =5 years before the first dose of study drugs and of low potential risk for recurrence. • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. • Adequately treated carcinoma in-situ without evidence of disease. 6. Patients with small-cell lung cancer or mixed small-cell lung cancer. 7. History of active primary immunodeficiency. 8. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBsAg result) and HCV. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. 9. Patients who have preoperative radiotherapy treatment as part of their care plan. 10. Patients who require or may require pneumonectomy, segmentectomies, or wedge resections, as assessed by their surgeon, to obtain potentially curative resection of primary tumor. 11. QTc interval = 470 ms (NOTE: If prolonged, then 2 additional ECGs should be obtained and the average QTcF interval should be used to determine eligibility). 12. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 13. Any medical contraindication to treatment with chemotherapy as listed in the local labelling. 14. Patients with moderate or severe cardiovascular disease: • Presence of cardiac disease, including myocardial infarction or unstable angina pectoris within 6 months prior to study entry. • NYHA Class 3 or 4 congestive heart failure, or uncontrolled hyperte
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To assess the antitumor activity of neoadjuvant treatment administered prior to surgery in terms of pathological Complete Response (pCR). -To assess the safety and tolerability of neoadjuvant and adjuvant treatment.;Secondary Objective: -To assess the efficacy of neoadjuvant treatment administered prior to surgery followed by adjuvant treatment post-surgery in terms of Event-Free Survival (EFS). -To assess the efficacy of neoadjuvant treatment administered prior to surgery followed by adjuvant treatment post-surgery in terms of Disease Free Survival (DFS) (event from surgery onwards) -To assess the feasibility of receiving the planned surgical tumor resection in patients receiving neoadjuvant treatment. -To assess the antitumor activity of neoadjuvant treatment administered prior to surgery in terms of major Pathological Response (mPR) -To assess the efficacy of neoadjuvant treatment administered prior to surgery in terms of Objective Response Rate (ORR) -To assess the efficacy of neoadjuvant and adjuvant treatment in terms of Overall Survival (OS). -To describe the PK of IPH5201 in combination with durvalumab +/- chemotherapy, in patients receiving neoadjuvant and adjuvant treatment.;Primary end point(s): -pCR is defined as lack of any viable tumor cells after complete evaluation in the resected lung cancer specimen and all sampled regional lymph nodes as determined by central independent pathological review and described by IASLC 20201. -Safety and tolerability will be evaluated in terms of Adverse Events (AEs), vital signs, and clinical laboratory.;Timepoint(s) of evaluation of this end point: -The measure of interest is the proportion of patients with 0% residual viable tumor cells within all resected tissue as assessed by the central pathologist. -Trough over the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -EFS is defined as time from neoadjuvant C1D1 to the first of the following: Documented local or distant recurrence of lung cancer as determined by Investigator using RECIST 1.1 assessment. Death due to any cause (event date is date of death). PD that precludes surgery (event date is the date of this determination) or PD discovered and reported by the Investigator upon attempting surgery (event date is the date of the first attempt at surgery). -DFS is defined as the time from the date of surgery until the first date of disease recurrence as determined by Investigator using RECIST 1.1 assessment (local or distant), or date of death due to any cause, whichever occurs first. Pathological confirmation from biopsied lesions will also be taken into consideration (as applicable). A new primary malignancy confirmed by pathology is not considered a DFS event. -Feasibility to surgery is defined as having the planned surgical resection within 40 days from the end of the last dose of neoadjuvant treatment. -mPR is defined as = 10% viable tumor cells in resected tumor after complete evaluation in the resected lung cancer specimen as determined by central independent pathological review as described by IASLC 2020 1. -OS is defined as the time from neoadjuvant C1D1 until the date of death due to any cause.;Timepoint(s) of evaluation of this end point: -The measure of interest is the median of EFS and landmark EFS at 12 months. -The measure of interest is the median of DFS and landmark DFS at 12 months. -The measure of interest is the proportion of patients that have intended surgery within 40 days from the end of last dose of neoadjuvant treatment. -The measure of interest is the proportion of patients with = 10% residual viable tumor cells within all resected tissue as assessed by the central pathologist. -The measure of interest is the median of the overall OS and landmark OS at 12 months. | — |
Countries
France, Greece, Hungary, Poland, United States
Contacts
Public ContactMedical Director
Innate Pharma SA
Outcome results
None listed