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

Non-small Cell Lung Cancer Clinical Trial

— NeoCOAST-2  

Official title:

A Phase II, Open-label, Multicentre, Randomised Study of Neoadjuvant and Adjuvant Treatment in Patients With Resectable, Early-stage (II to IIIB) Non-small Cell Lung Cancer (NeoCOAST-2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05061550
• Other study ID #: D9077C00001
• Secondary ID: 2023-508852-21-0
• Status: Recruiting
• Phase: Phase 2
• Start date: April 14, 2022
• Est. completion date: December 22, 2028

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 in combination with platinum doublet chemotherapy or datopotamab deruxtecan (Dato-DXd) in combination with durvalumab and single agent platinum chemotherapy in participants with resectable, early-stage non-small cell lung cancer.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 490
• Est. completion date: December 22, 2028
• Est. primary completion date: December 22, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

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.
• 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 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-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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Durvalumab
Participants will receive Durvalumab via intravenous route.
• Oleclumab
Participants will receive Oleclumab via intravenous route.
• Monalizumab
Participants will receive Monalizumab via intravenous route.
• Dato-DXd
Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.
• AZD0171
Participants will receive AZD0171 via intravenous route.
• Carboplatin
Carboplatin as chemotherapy
• Cisplatin
Cisplatin as chemotherapy
• Pemetrexed/Cisplatin
Pemetrexed/Cisplatin as chemotherapy
• Pemetrexed/Carboplatin
Pemetrexed/Carboplatin as chemotherapy
• Carboplatin/Paclitaxel
Carboplatin/Paclitaxel, as chemotherapy
• Volrustomig
Participants will receive Volrustomig via intravenous route.

Locations

Country	Name	City	State
Belgium	Research Site	Charleroi
Belgium	Research Site	Gent
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Belgium	Research Site	Roeselare
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montréal	Quebec
Canada	Research Site	Winnipeg	Manitoba
France	Research Site	Avignon Cedex
France	Research Site	Bobigny
France	Research Site	Bordeaux Cedex
France	Research Site	Limoges
France	Research Site	Rennes Cedex
France	Research Site	Rouen
France	Research Site	Suresnes
France	Research Site	Toulon
Hungary	Research Site	Kecskemét
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Tatabánya
Hungary	Research Site	Törökbálint
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin 7
Ireland	Research Site	Dublin 8
Ireland	Research Site	Galway
Italy	Research Site	Aviano
Italy	Research Site	Brescia
Italy	Research Site	Catanzaro
Italy	Research Site	Firenze
Italy	Research Site	Genova
Italy	Research Site	Meldola
Italy	Research Site	Milano
Italy	Research Site	Monza
Italy	Research Site	Padova
Italy	Research Site	Perugia
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Chungcheongbuk-do
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Korea, Republic of	Research Site	Suwon
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisbon
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Coruña
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Malaga
Spain	Research Site	Reus,Tarragona
Spain	Research Site	Sevilla
Spain	Research Site	Terrassa
Spain	Research Site	Valencia
Taiwan	Research Site	Liuying
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Buffalo	New York
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Fairfax	Virginia
United States	Research Site	Gainesville	Georgia
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Angeles	California
United States	Research Site	Memphis	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	Oakland	California
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Saint Louis Park	Minnesota
United States	Research Site	Seattle	Washington
United States	Research Site	Stuart	Florida

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Hungary,  Ireland,  Italy,  Korea, Republic of,  Portugal,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with pathological complete response (pCR)		From randomization to approximately 15 weeks after the first dose of study interventions
Primary	Number of participants with adverse events (AEs) and serious adverse events (SAEs)		Until Day 90 after the last dose of study interventions (Up to approximately 3 years)
Secondary	Number of participants experiencing an event-free survival (EFS) event		Up to approximately 3 years
Secondary	Number of participants experiencing a disease-free survival (DFS) event		Up to approximately 3 years
Secondary	Number of participants having surgical resection		From randomization to approximately 15 weeks after the first dose of study interventions
Secondary	Number of participants with major pathological response (mPR)		From randomization to approximately 15 weeks after the first dose of study interventions
Secondary	Number of participants with Objective response rate (ORR)		From randomization to approximately 15 weeks after the first dose of study interventions
Secondary	Overall survival (OS)		Up to approximately 3 years
Secondary	Serum concentration of study interventions (Durvalumab/Oleclumab/Monalizumab/Volrustomig)		From randomization to last dose of study interventions (Up to approximately 3 Years)
Secondary	Number of participants with anti-study drug antibodies (ADA)		From randomization to 3 months after last dose of study interventions (Up to approximately 3 Years)
Secondary	Baseline PD-L1 expression		At Screening/ baseline
Secondary	Changes in circulating tumour DNA (ctDNA)		From randomization to up to 24 months after last dose of study interventions (Up to approximately 3 Years)