Recruiting
Phase 2

Neoadjuvant & Adjuvant

Sponsor:

AstraZeneca

Code:

NCT05061550

Conditions

Non-small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Durvalumab

Oleclumab

Monalizumab

Dato-DXd

AZD0171

Study Details

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.

Conditions

Non-small Cell Lung Cancer

Study ID

NCT05061550

Start date

Apr 14, 2022

Status verified date

Aug, 2026

Completion date

May 28, 2030

Anticipated

Primary completion date

May 28, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

630 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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

experimental: 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

experimental: 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

experimental: 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

experimental: 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

experimental: 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

experimental: 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

Interventions

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.

Rilvegostomig

Participants will receive Rilvegostomig via intravenous route.

Primary outcome measure

  • Number of participants with pathological complete response (pCR) [ Time Frame: From randomization to approximately 15 weeks after the first dose of study interventions ]
  • Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Until Day 90 after the last dose of study interventions (Up to approximately 3 years) ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

AstraZeneca Lung Cancer Study Locator Service

1-884-432-3892az-lcsl@careboxhealth.com

Locations

Research Site

Recruiting

Little Rock, Arkansas, United States, 72205

Research Site

Recruiting

Los Angeles, California, United States, 90095

Research Site

Recruiting

New Haven, Connecticut, United States, 06510

Research Site

Recruiting

Chicago, Illinois, United States, 60637

Research Site

Recruiting

Baltimore, Maryland, United States, 21231

Research Site

Recruiting

Boston, Massachusetts, United States, 02215

Research Site

Recruiting

Omaha, Nebraska, United States, 68124

Research Site

Recruiting

Buffalo, New York, United States, 14263

Research Site

Recruiting

Cleveland, Ohio, United States, 44195

Research Site

Recruiting

Pittsburgh, Pennsylvania, United States, 15212

Research Site

Recruiting

Chattanooga, Tennessee, United States, 37404

Research Site

Recruiting

Memphis, Tennessee, United States, 38120

Research Site

Recruiting

Nashville, Tennessee, United States, 37203

Research Site

Recruiting

Nashville, Tennessee, United States, 37232

Research Site

Recruiting

Houston, Texas, United States, 77030

Research Site

Recruiting

Houston, Texas, United States, 77090

Research Site

Recruiting

Fairfax, Virginia, United States, 22031

Research Site

Recruiting

Edmonds, Washington, United States, 98026

Research Site

Recruiting

Seattle, Washington, United States, 98104

Research Site

Recruiting

Winnipeg, Manitoba, Canada, R3E 0V9

Research Site

Recruiting

Montreal, Quebec, Canada, H2W 1S6

Research Site

Recruiting

Montreal, Quebec, Canada, H2X 3E4

More Information

Sponsor

AstraZeneca

Last update posted

Aug 21, 2026

Last verified

Aug, 2026

Keywords

  • Lung Cancer
  • early-stage
  • Durvalumab
  • Oleclumab
  • Monalizumab
  • AZD0171
  • Datopotamab Deruxtecan
  • Neoadjuvant
  • Adjuvant
  • Chemotherapy
  • Volrustomig
  • Rilvegostomig

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-08-21.