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NCT Number: NCT05221840

A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer

This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Box Hill, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant must be ≥ 18 years at the time of screening.
  • Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
  • Provision of a tumour tissue sample obtained prior to CRT
  • Documented tumour PD-L1 status by central lab
  • Documented EGFR and ALK wild-type status (local or central).
  • Patients must not have progressed following definitive, platinum based, concurrent chemoradiotherapy
  • Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
  • Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
  • WHO performance status of 0 or 1 at randomization
  • Adequate organ and marrow function

Exclusion criteria

  • History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥5 years before the first dose of study intervention and of low potential risk for recurrence, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours without evidence of disease.
  • Mixed small cell and non-small cell lung cancer histology.
  • Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
  • Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
  • Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia).
  • Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
  • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis (≥ Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis - diagnosed in the past 6 months prior to randomization.
  • Active or prior documented autoimmune or inflammatory disorders (with exceptions)
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Treatment and study plan

Durvalumab

Drug

Durvalumab IV (intravenous infusion)

Oleclumab

Drug

Oleclumab IV (intravenous infusion)

Monalizumab

Drug

Monalizumab IV (intravenous infusion)

Placebo

Other

Placebo IV (intravenous infusion)

Primary outcomes

  1. Progression Free Surival (PFS)

    Time frame: Up to 5 years after first patient randomized.

    Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1.

Secondary outcomes

  1. Overall Survival (OS)

    Time frame: Up to 9 years after first patient randomized

    Overall survival (OS)

  2. Objective response rate (ORR)

    Time frame: Up to 5 years after first patient randomized

    Objective response rate (ORR) per RECIST 1.1 as assessed by BICR

  3. Overall survival (OS) at 24 months

    Time frame: Up to 9 years after first patient randomized

    Overall survival (OS) at 24 months

  4. Duration of response (DoR)

    Time frame: Up to 5 years after first patient randomized

    Duration of response (DoR) per RECIST 1.1 as assessed by BICR

  5. Progression free survival (PFS) at 6, 12, 18, and 24 months

    Time frame: From date of randomization until 24 months

    Progression free survival (PFS) at 6, 12, 18, and 24 months respectively, per RECIST 1.1 as assessed by BICR

  6. Time from randomization to second progression (PFS2)

    Time frame: Up to 5 years after first patient randomized

    Time from randomization to second progression (PFS2)

  7. Time from randomization to first date of distant metastasis or death (TTDM)

    Time frame: Up to 5 years after first patient randomized

    Time from randomization to first date of distant metastasis or death (TTDM)

  8. Time from randomization to start date of first subsequent therapy (TFST)

    Time frame: Up to 9 years after first patient randomized

    Time from randomization to start date of first subsequent therapy (TFST)

  9. Progression free survival (PFS) as assessed by Investigator

    Time frame: Up to 5 years after first patient randomized

    Progression free survival (PFS) as assessed by Investigator

  10. IHC analysis of PD-L1 TC expression

    Time frame: Up to 5 years after first patient randomized

    IHC analysis of PD-L1 TC expression relative to efficacy outcomes

  11. Concentration of Durvalumab

    Time frame: From date of randomization until 3 months after date of last IP dose

    To assess the Pharmacokinetics of Durvalumab when in combination with Monalizumab or Oleclumab - serum peak and trough concentrations

  12. Anti-drug antibodies (ADAs)

    Time frame: From date of randomization until 3 months after date of last IP dose

    The immunogenicity of durvalumab, oleclumab, and monalizumab as assessed by presence of anti-drug antibodies (ADAs)

  13. Time to deterioration in pulmonary symptoms (TTFCD)

    Time frame: Up to 5 years after last patient randomized

    Time to deterioration in pulmonary symptoms (TTFCD)

  14. Concentration of Oleclumab

    Time frame: From date of randomization until 3 months after last dose of IP

    To assess the Pharmacokinetics of Oleclumab when in combination with Durvulumab - serum peak and trough concentrations

  15. Concentration of Monalizumab

    Time frame: From date of randomization until 3 months after last dose of IP

    To assess the Pharmacokinetics of Monalizumab when in combination with Durvalumab - serum peak and trough concentrations

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

A Phase III, Double-blind, Placebo-controlled, Randomised, Multicentre, International Study of Durvalumab Plus Oleclumab and Durvalumab Plus Monalizumab in Patients With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Definitive, Platinum-Based Concurrent Chemoradiation Therapy

Acronym: PACIFIC-9

Important dates

Study start
2022
Primary completion
2026
Study completion
2030
First posted
Feb 3, 2022
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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