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NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05061550
Collaborator
Parexel (Industry)
140
Enrollment
49
Locations
2
Arms
47.5
Anticipated Duration (Months)
2.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is intended to assess the safety and efficacy of neoadjuvant Durvalumab in combination with chemotherapy and Oleclumab or Monalizumab and adjuvant treatment in participants with resectable, early-stage non-small cell lung cancer

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

In this open-label, 2-arms study, eligible participants will be enrolled and randomised in a 1:1 ratio to receive either Durvalumab + chemotherapy + Oleclumab before surgery followed by Durvalumab + Oleclumab post-surgery (Arm 1) or Durvalumab + chemotherapy + Monalizumab before surgery followed by Durvalumab + Monalizumab post-surgery (Arm 2). Surgical resection is to be performed approximately within 40 days from the last dose of neoadjuvant treatment.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
140 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Open-label, Multicentre, Randomised Study of Neoadjuvant and Adjuvant Treatment in Patients With Resectable, Early-stage (II to IIIA) Non-small Cell Lung Cancer (NeoCOAST 2)
Actual Study Start Date :
Apr 14, 2022
Anticipated Primary Completion Date :
Mar 30, 2026
Anticipated Study Completion Date :
Mar 30, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Durvalumab and Oleclumab

Participants will receive Durvalumab + Oleclumab + chemotherapy (every 3 weeks [Q3W]) followed by surgery. Post-surgery, participants will receive Durvalumab + Oleclumab (every 4 weeks [Q4W]), unless progression of disease (PD) or any withdrawal criteria are met.

Drug: Durvalumab
Participants will receive Durvalumab via intravenous route before surgery and after surgery.
Other Names:
  • MEDI4736, IMFINZI

    • Drug: Oleclumab
    Participants will receive Oleclumab via intravenous route before surgery and after surgery.
    Other Names:
  • MEDI9447

    		•
    Experimental: Durvalumab and Monalizumab

    Participants will receive Durvalumab + Monalizumab + chemotherapy (Q3W) followed by surgery. Post-surgery, participants will receive Durvalumab + Monalizumab (Q4W), unless PD or any withdrawal criteria are met.

    Drug: Durvalumab
    Participants will receive Durvalumab via intravenous route before surgery and after surgery.
    Other Names:
  • MEDI4736, IMFINZI

    • Drug: Monalizumab
    Participants will receive Monalizumab via intravenous route before surgery and after surgery.
    Other Names:
  • IPH2201

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of participants with pathological complete response (pCR) [Within 40 days of the last dose of study drug after cycle 4 (each cycle length is 21 days) (Up to approximately 3 Years)]

      pCR is determined by central blinded independent pathologist review (BIPR) and described by International Association for the Study of Lung Cancer (IASLC) 2020.

    2. Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Untill Day 90 after the last dose of study drugs (Up to approximately 3 years)]

      To assess safety and tolerability.

    Secondary Outcome Measures

    1. Number of participants experiencing an event-free survival (EFS) event [Up to approximately 3 years]

      Assessments of EFS will be done by investigator.

    2. Number of participants experiencing a disease-free survival (DFS) event [Up to approximately 3 years]

      Assessments of DFS will be done by investigator.

    3. Number of participants having surgical resection [Within 40 days of the last dose of study drug after cycle 4 (each cycle length is 21 days) (Up to approximately 3 Years)]

      Feasibility to surgery is defined as having the planned surgical resection within 40 days from the end of the last dose of neoadjuvant study drugs.

    4. Number of participants with major pathological response (mPR) [Within 40 days of the last dose of study drug after cycle 4 (each cycle length is 21 days) (Up to approximately 3 Years)]

      mPR is determined by central BIPR as described by IASLC 2020.

    5. Number of participants with Objective response rate (ORR) [Up to approximately 3 years]

      Assessments of ORR will be done by investigator.

    6. Overall survival (OS) [Up to approximately 3 years]

      Assessments of OS will be done by investigator.

    7. Serum concentration of study drugs (Durvalumab/Oleclumab/Monalizumab) [Pre-dose and post-dose of cycle 1 to 4 (21 days cycle) and cycle 1 to 12 (28 days cycle)]

      To measure the concentration of Durvalumab/Oleclumab/Monalizumab in serum as variable of pharmacokinetic parameter.

    8. Number of participants with anti-study drug antibodies (ADA) [Pre-dose and post-dose of cycle 1 to 4 (21 days cycle) and cycle 1 to 12 (28 days cycle)]

      To assess the presence of anti-drug antibody (ADA) for study drugs (Durvalumab/Oleclumab/Monalizumab) as variable of immunogenicity parameters.

    9. Baseline PD-L1 expression [At Screening/ baseline]

      The baseline PD-L1 expression in participants treated with neoadjuvant and adjuvant treatment, and associations with clinical endpoints will be investigated.

    10. Changes in circulating tumour DNA (ctDNA) [Pre-dose and post-dose of cycle 1 to 4 (21 days cycle) and cycle 1 to 12 (28 days cycle)]

      The changes in ctDNA during neoadjuvant treatment in participants with evaluable ctDNA and associations with clinical endpoints will be evaluated.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Newly diagnosed NSCLC patients with resectable disease (Stage IIA to Stage IIIA).

    • WHO or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    • Adequate organ and marrow function.

    • Provision of tumour samples (newly acquired or archival tumour tissue [≤ 6 months old]) to confirm Programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) status.

    • Participants will be suitable for inclusion if the planned surgery to be performed will be lobectomy, sleeve resection, or bilobectomy.

    • A pre- or post-bronchodilator forced expiratory volume in 1 (FEV1) of 1.0 L and diffusing capacity of the lungs for carbon monoxide (DLCO) > 40% postoperative predicted value.

    Exclusion Criteria:

    • Participants with sensitising EGFR mutations or ALK translocations.

    • History of allogeneic organ transplantation.

    • Active or prior documented autoimmune or inflammatory disorders.

    • Uncontrolled intercurrent illness, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement.

    • History of another primary malignancy.

    • Participants with small-cell lung cancer or mixed small-cell lung cancer.

    • History of active primary immunodeficiency.

    • Participants who have preoperative radiotherapy treatment as part of their care plan.

    • Participants who require or may require pneumonectomy, segmentectomies, or wedge resections, as assessed by their surgeon, to obtain potentially curative resection of primary tumour.

    • QTcF (QT interval corrected by Fridericia's formula) interval ≥ 470 ms.

    • Any medical contraindication to treatment with chemotherapy as listed in the local labelling.

    • Participants with moderate or severe cardiovascular disease:

    • Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment.

    • Receipt of live attenuated vaccine within 30 days prior to the first dose of study drugs.

    • Prior exposure to immune-mediated therapy. Participants who received agents targeting the adenosine pathway and anti-NKG2A agents are also excluded.

    • Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Saint Petersburg Florida United States 33705
    2 Research Site Baltimore Maryland United States 21231
    3 Research Site Boston Massachusetts United States 02215
    4 Research Site Saint Louis Park Minnesota United States 55426
    5 Research Site Cleveland Ohio United States 44195
    6 Research Site Pittsburgh Pennsylvania United States 15212
    7 Research Site Memphis Tennessee United States 38120
    8 Research Site Houston Texas United States 77030
    9 Research Site Fairfax Virginia United States 22031
    10 Research Site Edmonton Alberta Canada T6G 1Z2
    11 Research Site Montreal Quebec Canada H2X 3E4
    12 Research Site Montréal Quebec Canada H2W 1S6
    13 Research Site Bordeaux Cedex France 33076
    14 Research Site Limoges France 83000
    15 Research Site Rennes Cedex France 35000
    16 Research Site Rouen France 76031
    17 Research Site Suresnes France 92150
    18 Research Site Aviano Italy 33081
    19 Research Site Firenze Italy 50134
    20 Research Site Genova Italy 16100
    21 Research Site Meldola Italy 47014
    22 Research Site Monza Italy 20900
    23 Research Site Padova Italy 35128
    24 Research Site Perugia Italy 06156
    25 Research Site Pisa Italy 56124
    26 Research Site Roma Italy 00144
    27 Research Site Rozzano Italy 20089
    28 Research Site Busan Korea, Republic of 48108
    29 Research Site Chungcheongbuk-do Korea, Republic of 28644
    30 Research Site Seongnam-si Korea, Republic of 13496
    31 Research Site Seoul Korea, Republic of 03080
    32 Research Site Seoul Korea, Republic of 05505
    33 Research Site Suwon Korea, Republic of 16247
    34 Research Site Lisboa Portugal 1400-038
    35 Research Site Lisboa Portugal 1500-650
    36 Research Site Porto Portugal 4099-001
    37 Research Site Porto Portugal 4100-180
    38 Research Site Porto Portugal 4200-072
    39 Research Site Barcelona Spain 08035
    40 Research Site Barcelona Spain 08036
    41 Research Site Cordoba Spain 14004
    42 Research Site Coruña Spain 15006
    43 Research Site Madrid Spain 28040
    44 Research Site Majadahonda Spain 28250
    45 Research Site Malaga Spain 29010
    46 Research Site Reus,Tarragona Spain 43204
    47 Research Site Sevilla Spain 41009
    48 Research Site Terrassa Spain 08221
    49 Research Site Valencia Spain 46010

    Sponsors and Collaborators

    • AstraZeneca
    • Parexel

    Investigators

    • Principal Investigator: Tina Cascone, MD, MD Anderson Cancer Center Houston, TX 77030

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT05061550
    Other Study ID Numbers:
    • D9077C00001
    • 2021-003369-37
    First Posted:
    Sep 29, 2021
    Last Update Posted:
    Aug 5, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    Lung Cancer
    early-stage
    Durvalumab
    Oleclumab
    Monalizumab
    Neoadjuvant
    Adjuvant
    Chemotherapy
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Durvalumab

    Study Results

    No Results Posted as of Aug 5, 2022