Clinical trial NCT05061550: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Lung Cancer
early-stage
Durvalumab
Oleclumab
Monalizumab
AZD0171
Datopotamab Deruxtecan
Neoadjuvant
Adjuvant
Chemotherapy
Volrustomig
Rilvegostomig
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2021-09-29
Enrollment: 630
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with pathological complete response (pCR)
timeFrame: From randomization to approximately 15 weeks after the first dose of study interventions
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Until Day 90 after the last dose of study interventions (Up to approximately 3 years)
Secondary outcomes:
measure: Number of participants experiencing an event-free survival (EFS) event
timeFrame: Up to approximately 3 years
measure: Number of participants experiencing a disease-free survival (DFS) event
timeFrame: Up to approximately 3 years
measure: Number of participants having surgical resection
timeFrame: From randomization to approximately 15 weeks after the first dose of study interventions
measure: Number of participants with major pathological response (mPR)
timeFrame: From randomization to approximately 15 weeks after the first dose of study interventions
measure: Number of participants with Objective response rate (ORR)
timeFrame: From randomization to approximately 15 weeks after the first dose of study interventions
measure: Overall survival (OS)
timeFrame: Up to approximately 3 years
measure: Serum concentration of study interventions (Durvalumab/Oleclumab/Monalizumab/Volrustomig/Rilvegostomig)
timeFrame: From randomization to last dose of study interventions (Up to approximately 3 Years)
measure: Number of participants with anti-study drug antibodies (ADA)
timeFrame: From randomization to 3 months after last dose of study interventions (Up to approximately 3 Years)
measure: Baseline PD-L1 expression
timeFrame: At Screening/ baseline
measure: Changes in circulating tumour DNA (ctDNA)
timeFrame: From randomization to up to 24 months after last dose of study interventions (Up to approximately 3 Years)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Oakland
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Stuart
country: United States
facility: Research Site
state: Florida
city: Gainesville
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Saint Louis Park
country: United States
facility: Research Site
state: Minnesota
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Buffalo
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Charleroi
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Roeselare
country: Belgium
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montréal
country: Canada
facility: Research Site
state: Quebec
city: Avignon Cedex
country: France
facility: Research Site
city: Bobigny
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Limoges
country: France
facility: Research Site
city: Rennes Cedex
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Suresnes
country: France
facility: Research Site
city: Toulon
country: France
facility: Research Site
city: Kecskemét
country: Hungary
facility: Research Site
city: Székesfehérvár
country: Hungary
facility: Research Site
city: Tatabánya
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
facility: Research Site
city: Dublin 7
country: Ireland
facility: Research Site
city: Dublin 8
country: Ireland
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Galway
country: Ireland
facility: Research Site
city: Aviano
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Catanzaro
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Meldola
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Monza
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Perugia
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Chungcheongbuk-do
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisbon
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
city: Coruña
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Reus,Tarragona
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Terrassa
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Liuying
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
Study officials:
affiliation: MD Anderson Cancer Center Houston, TX 77030
name: Tina Cascone, MD
role: PRINCIPAL_INVESTIGATOR
References: