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

NCT ID: NCT05061550

Last Updated: 2025-12-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

630 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-14

Study Completion Date

2030-05-09

Brief Summary

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The study is intended to assess the safety and efficacy of perioperative treatment with Durvalumab in combination with Oleclumab, Monalizumab, or AZD0171 and platinum doublet chemotherapy (CTX); or Volrustomig or Rilvegostomig in combination with CTX; or Datopotamab deruxtecan (Dato-DXd) in combination with Durvalumab or Rilvegostomig and single agent platinum chemotherapy in participants with resectable, early-stage non-small cell lung cancer.

Detailed Description

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This is an open-label, multi-arms, multicentre, randomised study, eligible participants will be enrolled and randomised to one of the following treatment regimens.

Arm 1: Participants will receive Oleclumab + durvalumab + CTX as neoadjuvant treatment and Oleclumab + durvalumab as adjuvant treatment.

Arm 2: Participants will receive Monalizumab + durvalumab + CTX as neoadjuvant treatment and Monalizumab + durvalumab as adjuvant treatment.

Arm 3: Participants will receive Volrustomig (Dose Exploration) + CTX as neoadjuvant treatment and Volrustomig as adjuvant treatment.

Arm 4: Participants will receive Dato-DXd + durvalumab + single agent platinum chemotherapy as neoadjuvant treatment and durvalumab as adjuvant treatment.

Arm 5: Participants will receive AZD0171 + durvalumab + CTX as neoadjuvant treatment and AZD0171 + durvalumab as adjuvant treatment.

Arm 6: Participants will receive Rilvegostomig + CTX as neoadjuvant treatment and Rilvegostomig as adjuvant treatment.

Arm 7: Participants will receive Dato-DXd + Rilvegostomig + single agent platinum chemotherapy as neoadjuvant treatment and Rilvegostomig as adjuvant treatment.

Conditions

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Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1: Oleclumab + Durvalumab + Platinum doublet chemotherapy (CTX)

Participants will receive Durvalumab + Oleclumab + CTX as neoadjuvant treatment and Durvalumab + Oleclumab as adjuvant treatment.

Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:

Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Group Type EXPERIMENTAL

Pemetrexed/Cisplatin

Intervention Type DRUG

Pemetrexed/Cisplatin as chemotherapy

Pemetrexed/Carboplatin

Intervention Type DRUG

Pemetrexed/Carboplatin as chemotherapy

Carboplatin/Paclitaxel

Intervention Type DRUG

Carboplatin/Paclitaxel, as chemotherapy

Durvalumab

Intervention Type DRUG

Participants will receive Durvalumab via intravenous route.

Oleclumab

Intervention Type DRUG

Participants will receive Oleclumab via intravenous route.

Arm 2: Monalizumab + Durvalumab + CTX

Participants will receive Durvalumab + Monalizumab + CTX as neoadjuvant treatment and Durvalumab + Monalizumab as adjuvant treatment.

Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:

Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Group Type EXPERIMENTAL

Pemetrexed/Cisplatin

Intervention Type DRUG

Pemetrexed/Cisplatin as chemotherapy

Pemetrexed/Carboplatin

Intervention Type DRUG

Pemetrexed/Carboplatin as chemotherapy

Carboplatin/Paclitaxel

Intervention Type DRUG

Carboplatin/Paclitaxel, as chemotherapy

Durvalumab

Intervention Type DRUG

Participants will receive Durvalumab via intravenous route.

Monalizumab

Intervention Type DRUG

Participants will receive Monalizumab via intravenous route.

Arm 3: Volrustomig (Dose Exploration) + CTX

Participants will receive Volrustomig + CTX as neoadjuvant treatment and Volrustomig as adjuvant treatment.

Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:

Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Group Type EXPERIMENTAL

Pemetrexed/Cisplatin

Intervention Type DRUG

Pemetrexed/Cisplatin as chemotherapy

Pemetrexed/Carboplatin

Intervention Type DRUG

Pemetrexed/Carboplatin as chemotherapy

Carboplatin/Paclitaxel

Intervention Type DRUG

Carboplatin/Paclitaxel, as chemotherapy

Volrustomig

Intervention Type DRUG

Participants will receive Volrustomig via intravenous route.

Arm 4: Dato-DXd + durvalumab + single agent platinum

Participants will receive Dato-DXd + durvalumab + single agent platinum as neoadjuvant treatment and durvalumab as adjuvant treatment.

Participants will receive one of the following chemotherapy regimens, based on physician choice of as part of their treatment regimen prior to surgery:

Carboplatin or Cisplatin

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Carboplatin as chemotherapy

Cisplatin

Intervention Type DRUG

Cisplatin as chemotherapy

Durvalumab

Intervention Type DRUG

Participants will receive Durvalumab via intravenous route.

Dato-DXd

Intervention Type DRUG

Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.

Arm 5: AZD0171 + durvalumab + CTX

Participants will receive AZD0171 + durvalumab + CTX as neoadjuvant treatment and AZD0171 + durvalumab as adjuvant treatment.

Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:

Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Group Type EXPERIMENTAL

AZD0171

Intervention Type DRUG

Participants will receive AZD0171 via intravenous route.

Pemetrexed/Cisplatin

Intervention Type DRUG

Pemetrexed/Cisplatin as chemotherapy

Pemetrexed/Carboplatin

Intervention Type DRUG

Pemetrexed/Carboplatin as chemotherapy

Carboplatin/Paclitaxel

Intervention Type DRUG

Carboplatin/Paclitaxel, as chemotherapy

Durvalumab

Intervention Type DRUG

Participants will receive Durvalumab via intravenous route.

Arm 6: Rilvegostomig + CTX

Participants will receive Rilvegostomig + CTX as neoadjuvant treatment and Rilvegostomig as adjuvant treatment.

Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:

Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Group Type EXPERIMENTAL

Pemetrexed/Cisplatin

Intervention Type DRUG

Pemetrexed/Cisplatin as chemotherapy

Pemetrexed/Carboplatin

Intervention Type DRUG

Pemetrexed/Carboplatin as chemotherapy

Carboplatin/Paclitaxel

Intervention Type DRUG

Carboplatin/Paclitaxel, as chemotherapy

Rilvegostomig

Intervention Type DRUG

Participants will receive Rilvegostomig via intravenous route.

Arm 7: Dato-DXd + Rilvegostomig + single agent platinum

Participants will receive Dato-DXd + Rilvegostomig + single agent platinum as neoadjuvant treatment and Rilvegostomig as adjuvant treatment.

Participants will receive one of the following chemotherapy regimens, based on physician choice of as part of their treatment regimen prior to surgery:

Carboplatin or Cisplatin

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Carboplatin as chemotherapy

Cisplatin

Intervention Type DRUG

Cisplatin as chemotherapy

Rilvegostomig

Intervention Type DRUG

Participants will receive Rilvegostomig via intravenous route.

Dato-DXd

Intervention Type DRUG

Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.

Interventions

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AZD0171

Participants will receive AZD0171 via intravenous route.

Intervention Type DRUG

Carboplatin

Carboplatin as chemotherapy

Intervention Type DRUG

Cisplatin

Cisplatin as chemotherapy

Intervention Type DRUG

Pemetrexed/Cisplatin

Pemetrexed/Cisplatin as chemotherapy

Intervention Type DRUG

Pemetrexed/Carboplatin

Pemetrexed/Carboplatin as chemotherapy

Intervention Type DRUG

Carboplatin/Paclitaxel

Carboplatin/Paclitaxel, as chemotherapy

Intervention Type DRUG

Volrustomig

Participants will receive Volrustomig via intravenous route.

Intervention Type DRUG

Rilvegostomig

Participants will receive Rilvegostomig via intravenous route.

Intervention Type DRUG

Durvalumab

Participants will receive Durvalumab via intravenous route.

Intervention Type DRUG

Oleclumab

Participants will receive Oleclumab via intravenous route.

Intervention Type DRUG

Monalizumab

Participants will receive Monalizumab via intravenous route.

Intervention Type DRUG

Dato-DXd

Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.

Intervention Type DRUG

Other Intervention Names

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MEDI4736, IMFINZI MEDI9447 IPH2201 MEDI5752

Eligibility Criteria

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Inclusion Criteria

* Newly diagnosed NSCLC patients with resectable disease (Stage IIA to Stage IIIB).
* WHO or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ and bone 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.
* Adequate pulmonary function.

Exclusion Criteria

* Participants with sensitising EGFR mutations or ALK translocations.
* Participants with baseline PD-L1 expression status \<1% (Arms 6 and 7 only).
* Active or prior documented autoimmune or inflammatory disorders.
* Uncontrolled intercurrent illness, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active bleeding diseases, 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.
* History of non-infectious interstitial lung disease (ILD) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
* 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 at baseline, 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 interventions.
* Prior exposure to approved or investigational immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-TIGIT (T cell immunoreceptor with Ig and ITIM domains), anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies. Participants who received agents targeting the adenosine pathway, anti-NKG2A, anti-HLA-E agents, and anti-LIF agents are also excluded. Participants who have received previous treatment with a TROP2 targeting ADC or with another ADC containing a chemotherapy agent that inhibits TOP1 activity are also excluded.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of study interventions.
* Active or uncontrolled infections including HBA, HBV, HCV, and HIV.
Minimum Eligible Age

18 Years

Maximum Eligible Age

95 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Parexel

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tina Cascone, MD

Role: PRINCIPAL_INVESTIGATOR

MD Anderson Cancer Center Houston, TX 77030

Locations

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Research Site

Little Rock, Arkansas, United States

Site Status RECRUITING

Research Site

Los Angeles, California, United States

Site Status RECRUITING

Research Site

Oakland, California, United States

Site Status WITHDRAWN

Research Site

New Haven, Connecticut, United States

Site Status RECRUITING

Research Site

Stuart, Florida, United States

Site Status COMPLETED

Research Site

Gainesville, Georgia, United States

Site Status COMPLETED

Research Site

Chicago, Illinois, United States

Site Status RECRUITING

Research Site

Baltimore, Maryland, United States

Site Status WITHDRAWN

Research Site

Baltimore, Maryland, United States

Site Status RECRUITING

Research Site

Boston, Massachusetts, United States

Site Status RECRUITING

Research Site

Saint Louis Park, Minnesota, United States

Site Status COMPLETED

Research Site

Omaha, Nebraska, United States

Site Status NOT_YET_RECRUITING

Research Site

Buffalo, New York, United States

Site Status RECRUITING

Research Site

Cleveland, Ohio, United States

Site Status RECRUITING

Research Site

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Research Site

Chattanooga, Tennessee, United States

Site Status RECRUITING

Research Site

Memphis, Tennessee, United States

Site Status RECRUITING

Research Site

Nashville, Tennessee, United States

Site Status RECRUITING

Research Site

Nashville, Tennessee, United States

Site Status NOT_YET_RECRUITING

Research Site

Nashville, Tennessee, United States

Site Status RECRUITING

Research Site

Houston, Texas, United States

Site Status RECRUITING

Research Site

Houston, Texas, United States

Site Status RECRUITING

Research Site

Fairfax, Virginia, United States

Site Status RECRUITING

Research Site

Edmonds, Washington, United States

Site Status RECRUITING

Research Site

Seattle, Washington, United States

Site Status RECRUITING

Research Site

Charleroi, , Belgium

Site Status RECRUITING

Research Site

Ghent, , Belgium

Site Status RECRUITING

Research Site

Ghent, , Belgium

Site Status COMPLETED

Research Site

Leuven, , Belgium

Site Status COMPLETED

Research Site

Roeselare, , Belgium

Site Status RECRUITING

Research Site

Edmonton, Alberta, Canada

Site Status COMPLETED

Research Site

Winnipeg, Manitoba, Canada

Site Status RECRUITING

Research Site

Montreal, Quebec, Canada

Site Status RECRUITING

Research Site

Montreal, Quebec, Canada

Site Status RECRUITING

Research Site

Avignon, , France

Site Status RECRUITING

Research Site

Bobigny, , France

Site Status WITHDRAWN

Research Site

Bordeaux, , France

Site Status COMPLETED

Research Site

Limoges, , France

Site Status RECRUITING

Research Site

Rennes, , France

Site Status RECRUITING

Research Site

Rouen, , France

Site Status RECRUITING

Research Site

Suresnes, , France

Site Status RECRUITING

Research Site

Toulon, , France

Site Status RECRUITING

Research Site

Kecskemét, , Hungary

Site Status RECRUITING

Research Site

Székesfehérvár, , Hungary

Site Status RECRUITING

Research Site

Tatabánya, , Hungary

Site Status COMPLETED

Research Site

Törökbálint, , Hungary

Site Status RECRUITING

Research Site

Dublin, , Ireland

Site Status RECRUITING

Research Site

Dublin, , Ireland

Site Status RECRUITING

Research Site

Dublin, , Ireland

Site Status RECRUITING

Research Site

Galway, , Ireland

Site Status RECRUITING

Research Site

Aviano, , Italy

Site Status RECRUITING

Research Site

Brescia, , Italy

Site Status RECRUITING

Research Site

Catanzaro, , Italy

Site Status WITHDRAWN

Research Site

Florence, , Italy

Site Status RECRUITING

Research Site

Genova, , Italy

Site Status RECRUITING

Research Site

Meldola, , Italy

Site Status RECRUITING

Research Site

Milan, , Italy

Site Status RECRUITING

Research Site

Monza, , Italy

Site Status RECRUITING

Research Site

Padua, , Italy

Site Status RECRUITING

Research Site

Perugia, , Italy

Site Status RECRUITING

Research Site

Pisa, , Italy

Site Status RECRUITING

Research Site

Roma, , Italy

Site Status RECRUITING

Research Site

Rozzano, , Italy

Site Status RECRUITING

Research Site

Lisbon, , Portugal

Site Status RECRUITING

Research Site

Lisbon, , Portugal

Site Status RECRUITING

Research Site

Lisbon, , Portugal

Site Status RECRUITING

Research Site

Lisbon, , Portugal

Site Status RECRUITING

Research Site

Porto, , Portugal

Site Status WITHDRAWN

Research Site

Porto, , Portugal

Site Status COMPLETED

Research Site

Porto, , Portugal

Site Status RECRUITING

Research Site

Busan, , South Korea

Site Status COMPLETED

Research Site

Chungcheongbuk-do, , South Korea

Site Status WITHDRAWN

Research Site

Seongnam-si, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Suwon, , South Korea

Site Status RECRUITING

Research Site

Suwon, , South Korea

Site Status RECRUITING

Research Site

A Coruña, , Spain

Site Status RECRUITING

Research Site

Alicante, , Spain

Site Status RECRUITING

Research Site

Barcelona, , Spain

Site Status RECRUITING

Research Site

Barcelona, , Spain

Site Status RECRUITING

Research Site

Córdoba, , Spain

Site Status RECRUITING

Research Site

Madrid, , Spain

Site Status RECRUITING

Research Site

Majadahonda, , Spain

Site Status RECRUITING

Research Site

Málaga, , Spain

Site Status RECRUITING

Research Site

Reus, , Spain

Site Status RECRUITING

Research Site

Seville, , Spain

Site Status RECRUITING

Research Site

Terrassa, , Spain

Site Status RECRUITING

Research Site

Valencia, , Spain

Site Status RECRUITING

Research Site

Liuying, , Taiwan

Site Status RECRUITING

Research Site

New Taipei City, , Taiwan

Site Status RECRUITING

Research Site

Tainan, , Taiwan

Site Status RECRUITING

Research Site

Taipei, , Taiwan

Site Status RECRUITING

Research Site

Taipei, , Taiwan

Site Status RECRUITING

Research Site

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Izmir, , Turkey (Türkiye)

Site Status RECRUITING

Countries

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United States Belgium Canada France Hungary Ireland Italy Portugal South Korea Spain Taiwan Turkey (Türkiye)

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

1-877-240-9479

AstraZeneca Lung Cancer Study Locator Service

Role: CONTACT

1-884-432-3892

References

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Cascone T, Bonanno L, Guisier F, Insa A, Liberman M, Bylicki O, Livi L, Egenod T, Corre R, Kim DW, Garcia Campelo MR, Provencio Pulla M, Shim BY, Metro G, Bennouna J, Bielska AA, Yohannes AR, He Y, Dowson A, Kar G, McGrath L, Kumar R, Grenga I, Spicer J, Forde PM. Perioperative durvalumab plus chemotherapy plus new agents for resectable non-small-cell lung cancer: the platform phase 2 NeoCOAST-2 trial. Nat Med. 2025 Aug;31(8):2788-2796. doi: 10.1038/s41591-025-03746-z. Epub 2025 May 31.

Reference Type DERIVED
PMID: 40450142 (View on PubMed)

Related Links

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https://www.lungcancerstudylocator.com/trial/listing/305617

Lung Cancer Study Locator details (for US)

Other Identifiers

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D9077C00001

Identifier Type: -

Identifier Source: org_study_id

2023-508852-21-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-003369-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

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