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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Innate Pharma

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Mar 2023 → ongoing

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Innate Pharma SA, France

External identifiers

EU CT number

2023-507778-42-00

EudraCT number

2022-001903-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Therapy, Safety

1. To assess the antitumor activity of neoadjuvant treatment administered prior to surgery in terms of pathological Complete Response (pCR).2.To assess the safety and tolerability of neoadjuvant treatment (Cohort 1 and Cohort 2) and adjuvant treatment (Cohort 1 only).

Secondary objectives 8

1. 1. To assess the efficacy of neoadjuvant treatment administered prior to surgery followed by adjuvant treatment post-surgery in terms of Event-Free Survival (EFS)(Cohort 1 only).
2. 2. 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) (Cohort 1 only)
3. 3. To assess the feasibility of receiving the planned surgical tumor resection in patients receiving neoadjuvant treatment.
4. 4. To assess the antitumor activity of neoadjuvant treatment administered prior to surgery in terms of major Pathological Response (mPR)
5. 5. To assess the efficacy of neoadjuvant treatment administered prior to surgery in terms of Objective Response Rate (ORR)
6. 6. To assess the efficacy of neoadjuvant treatment administered prior to surgery, followed by adjuvant treatment post-surgery in terms of Overall Survival (OS) (Cohort 1 only)
7. 7. To describe the PK of IPH5201 in combination with durvalumab +/- chemotherapy, in patients receiving neoadjuvant treatment (Cohort 1 and Cohort 2) and adjuvant treatment (Cohort 1)
8. 8. To assess the immunogenicity of IPH5201, in combination with durvalumab +/- chemotherapy, in patients receiving neoadjuvant treatment (Cohort 1 and Cohort 2) and adjuvant treatment (Cohort 1)

Conditions and MedDRA coding

Non-Small Cell Lung Cancer II, III

Study design 6 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. 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.
2. 2. 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.
3. 3. Age: Patients must be ≥ 18 years at the time of screening.
4. 4. 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)
5. 5. Type of Participant and Disease Characteristics: WHO PS or ECOG PS of 0 or 1 at enrolment
6. 6. 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.
7. 7. Type of Participant and Disease Characteristics: Must have a life expectancy of at least 12 weeks.
8. 8. Weight: Body weight > 35 kg.
9. 9. Sex: Male and/or female.
10. 10. Sex: Negative pregnancy test (serum or urine) for women of childbearing potential.
11. 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.
12. 12. Tumor sample requirements: Provision of tumor samples appropriate for exploratory biomarker analyses
13. 13. 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.
14. 14. 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.

Exclusion criteria 27

1. 1. Medical Conditions: Patients with sensitizing EGFR mutations or ALK translocations.
2. 11. 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.
3. 12. 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).
4. 13. Medical Conditions: Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
5. 14. Medical Conditions: Any medical contraindication to treatment with chemotherapy as listed in the local labelling.
6. 15. 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.
7. 16. 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.
8. 17. 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.
9. 18. Prior/Concomitant Therapy: Major surgical procedure (as defined by the Investigator) within 30 days prior to the first dose of study drugs.
10. 19. 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.
11. 20. 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).
12. 2. Medical Conditions: History of allogeneic organ transplantation.
13. 21. Prior/concurrent clinical study experience: Participation in another clinical study with an investigational product administered within 30 days prior to enrollment.
14. 22. Prior/concurrent clinical study experience: Previous study drugs (durvalumab, IPH5201) assignment in the present study.
15. 23. 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.
16. 24. Other Exclusions: Involvement in the planning and/or conduct of the study (applies to both company staff and/or staff at the study site).
17. 25. 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.
18. 26. Other Exclusions: Exclusion criteria for participation in the optional (DNA) genetics research component
19. 3. 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.
20. 4. 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.
21. 5. 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.
22. 6. 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
23. 8. Medical Conditions: History of active primary immunodeficiency.
24. 9. 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.
25. 10. Medical Conditions: Patients who have preoperative radiotherapy treatment as part of their care plan.
26. 7. Medical Conditions: Patients with small-cell lung cancer or mixed small-cell lung cancer.
27. 27. Other Exclusions: Only for patients in Cohort 2: Patients with PD-L1 expression TPS < 1% or unknown PD-L1 status

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.. The measure of interest is the proportion of patients with0% residual viable tumor cells within all resected tissue as assessed by the central pathologist. -Safety and tolerability will be evaluated in terms of adverse events, vital signs, and clinical laboratory.

Secondary endpoints 7

1. 1. EFS is defined as the time from neoadjuvant Cycle 1 Day 1 to the first of the following: -Documented local or distant recurrence of lung cancer as determined by the Investigator using RECIST 1.1 assessment. -Death due to any cause (event date is date of death).
2. 2. EFS is defined as the time from neoadjuvant Cycle 1 Day 1 to the first of the following: 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). The measure of interest is the median of EFS and landmark EFS at 12 months
3. 3. 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)..
4. 4. Feasibility to surgery is defined as having the planned surgical resection within 40 days from the end of the last dose of neoadjuvant treatment. The measure of interest is the proportion of patients who have intended surgery within 40 days from the end of last dose of neoadjuvant treatment.
5. 5. 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 and described by IASLC 2020). 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.
6. 7. OS is defined as the time from neoadjuvant Cycle 1 Day 1 until the date of death due to any cause. The measure of interest is the median of the overall OS and landmark OS at 12 months.
7. 6. ORR is defined as the proportion of patients who have a complete response (CR) or partial response (PR)), as determined by Investigator using RECIST 1.1. Data obtained from neoadjuvant Cycle 1 Day 1 up until surgery, or the last evaluable assessment in the absence of progression, prior to surgery, will be included in the assessment of ORR, regardless of whether the patient withdraws therapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Innate Pharma

Sponsor organisation

Innate Pharma

Address

117 Avenue De Luminy

City

Marseille

Postcode

13009

Country

France

Scientific contact point

Organisation

Innate Pharma

Contact name

Regulatory Affairs

Public contact point

Organisation

Innate Pharma

Contact name

Regulatory Affairs

Third parties 11

Locations

4 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications