Study of pre- and post-surgery treatment with IPH5201 and durvalumab in participants with lung cancer (MATISSE)

Prior treatment

• Prior/Concomitant Therapy: Prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies. Patients who received agents targeting the adenosine pathway (e.g., anti-CD73, A2AR inhibitors, anti-CD39 antibody) are also excluded.
• Prior/Concomitant Therapy: Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs. The following are exceptions to this criterion: • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection). • Systemic corticosteroids ≤ 12 mg/day of prednisone or its equivalent. • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Prior/concurrent clinical study experience: Participation in another clinical study with an investigational product administered within 30 days prior to enrollment.
• Prior/concurrent clinical study experience: Previous study drugs (durvalumab, IPH5201) assignment in the present study.
• Other Exclusions: Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of study drugs administration.
• Medical Conditions: 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. • 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.
• Medical Conditions: 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.
• Medical Conditions: 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
• Medical Conditions: Any medical contraindication to treatment with chemotherapy as listed in the local labelling.
• Medical Conditions: 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 hypertension. • History of hypertensive crisis/hypertensive encephalopathy within 6 months prior to the scheduled first dose of study drugs.
• Prior/Concomitant Therapy: Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment.Hoerver, concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Prior/Concomitant Therapy: Receipt of live attenuated vaccine within 30 days prior to the first dose of study drugs. Note: If enrolled, patients should not be administered live vaccine while receiving study drugs and up to 30 days after the last dose of study drugs.
• Prior/Concomitant Therapy: Major surgical procedure (as defined by the Investigator) within 30 days prior to the first dose of study drugs.

Other illness

• Medical Conditions: History of allogeneic organ transplantation.
• Medical Conditions: Patients who require or may require pneumonectomy, segmentectomies, or wedge resections, as assessed by their surgeon, to obtain potentially curative resection of primary tumor.
• Medical Conditions: 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 diarrhea, 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.
• Medical Conditions: History of active primary immunodeficiency.
• Medical Conditions: 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.
• Medical Conditions: Patients who have preoperative radiotherapy treatment as part of their care plan.
• Medical Conditions: Patients with small-cell lung cancer or mixed small-cell lung cancer.
• Medical Conditions: Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Lab values

• Medical Conditions: Patients with sensitizing EGFR mutations or ALK translocations.
• Medical Conditions: 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).

Other

• Other Exclusions: Involvement in the planning and/or conduct of the study (applies to both company staff and/or staff at the study site).
• Other Exclusions: Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
• Other Exclusions: Exclusion criteria for participation in the optional (DNA) genetics research component
• Other Exclusions: Only for patients in Cohort 2: Patients with PD-L1 expression TPS < 1% or unknown PD-L1 status

• Informed consent: 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.
• Sex: Negative pregnancy test (serum or urine) for women of childbearing potential.
  • 11 Tumor sample requirements: 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.
• Tumor sample requirements: Provision of tumor samples appropriate for exploratory biomarker analyses
• Surgery eligibility (assessments performed at screening): Patients are suitable for inclusion if the planned surgery to be performed is 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.
• Surgery eligibility (assessments performed at screening): 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.
• Informed consent: 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.
• Age: Patients must be ≥ 18 years at the time of screening.
• Type of Participant and Disease Characteristics : Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC. Patients should have resectable (Stage IIA to Stage IIIA; Stage IIIB – Nodal stage N2 after the first 40 patients [cohort 2]), according to Version 8 of IASLC Staging Manual in Thoracic Oncology (2016), and be candidates for lobectomy, sleeve reection, or bilobectomy at the time of screening. For patients with N2 disease, only those with 1 single nodal station ≤ 3 cm are eligible)(only valid for Cohort 1)
• Type of Participant and Disease Characteristics: WHO PS or ECOG PS of 0 or 1 at enrolment
• Type of Participant and Disease Characteristics: 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 upon 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.
• Type of Participant and Disease Characteristics: Must have a life expectancy of at least 12 weeks.
• Weight: Body weight > 35 kg.
• Sex: Male and/or female.