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

NCT05221840
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Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
1,051
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Lead sponsor
AstraZeneca
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Start date
2022-02-07
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Number of sites
202
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Summary
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.
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Acronym
PACIFIC-9
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Short title
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
clinicaltrials.gov
Official 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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2030-07-02
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First posted
2022-02-03
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Registry last updated
2026-06-18
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Primary completion date
2026-09-30
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Start date
2022-02-07
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Actual participants
1,051
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Participants
1,051
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Participant count basis
Actual
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Protocol amendments
5
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Number of sites
202
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05221840
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ClinicalTrials.gov ID
NCT05221840
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masking description
Double-Blind
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Progression Free Surival (PFS)

    Timeframe: Up to 5 years after first patient randomized.

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

  1. Overall Survival (OS)

    Timeframe: Up to 9 years after first patient randomized

    Overall survival (OS)

  2. Objective response rate (ORR)

    Timeframe: 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

    Timeframe: Up to 9 years after first patient randomized

    Overall survival (OS) at 24 months

  4. Duration of response (DoR)

    Timeframe: 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

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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

    Timeframe: Up to 5 years after first patient randomized

    Progression free survival (PFS) as assessed by Investigator

  10. IHC analysis of PD-L1 TC expression

    Timeframe: Up to 5 years after first patient randomized

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

  11. Concentration of Durvalumab

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: Up to 5 years after last patient randomized

    Time to deterioration in pulmonary symptoms (TTFCD)

  14. Concentration of Oleclumab

    Timeframe: 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

    Timeframe: 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

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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.
Sources for eligibility
clinicaltrials.gov

  • Research SiteSan Diego, United States
  • Research SiteNew Haven, United States
  • Research SiteStuart, United States
  • Research SiteUrbana, United States
  • Research SiteNew Albany, United States
  • Research SiteLexington, United States
  • Research SiteLouisville, United States
  • Research SiteAnnapolis, United States
  • Research SiteBaltimore, United States
  • Research SiteBaltimore, United States
  • Research SiteBethesda, United States
  • Research SiteGrand Rapids, United States
  • Research SiteDuluth, United States
  • Research SiteBillings, United States
  • Research SiteRidgewood, United States
  • Research SiteIthaca, United States
  • Research SiteGreensboro, United States
  • Research SiteCleveland, United States
  • Research SiteCleveland, United States
  • Research SiteMaumee, United States
  • Research SitePortland, United States
  • Research SitePhiladelphia, United States
  • Research SiteYork, United States
  • Research SiteSioux Falls, United States
  • Research SiteHouston, United States

And 177 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2021-004346-37
  • 2023-503999-24-00
Sources for references
clinicaltrials.gov

Related records

Drugs (3)

Lead sponsors (1)

Conditions (1)

Targets (3)