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 (PACIFIC-9)

• ClinicalTrials.gov Identifier: NCT05221840
• Recruitment Status: Recruiting
• First Posted: February 3, 2022
• Last Update Posted: April 16, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: January 14, 2022
• First Posted Date: February 3, 2022
• Last Update Posted Date: April 16, 2024
• Actual Study Start Date: February 7, 2022
• Estimated Primary Completion Date: May 29, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 2, 2022)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 11, 2022)

• Overall Survival (OS) [ Time Frame: Up to 9 years after first patient randomized ]
  Overall survival (OS)
• 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
• Overall survival (OS) at 24 months [ Time Frame: Up to 9 years after first patient randomized ]
  Overall survival (OS) at 24 months
• 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
• 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
• Time from randomization to second progression (PFS2) [ Time Frame: Up to 5 years after first patient randomized ]
  Time from randomization to second progression (PFS2)
• 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)
• 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)
• 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
• 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
• 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
• 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)
• Time to deterioration in pulmonary symptoms (TTFCD) [ Time Frame: Up to 5 years after last patient randomized ]
  Time to deterioration in pulmonary symptoms (TTFCD)
• 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
• 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

Original Secondary Outcome Measures (submitted: February 2, 2022)

• Overall Survival (OS) [ Time Frame: Up to 9 years after first patient randomized ]
  Overall survival (OS)
• 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
• Overall survival (OS) at 24 months [ Time Frame: Up to 9 years after first patient randomized ]
  Overall survival (OS) at 24 months
• 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
• Progression free survival (PFS) at 6, 12, 18, and 24 months [ Time Frame: Up to 5 years after first patient randomized ]
  Progression free survival (PFS) at 6, 12, 18, and 24 months respectively, per RECIST 1.1 as assessed by BICR
• Time from randomization to second progression (PFS2) [ Time Frame: Up to 5 years after first patient randomized ]
  Time from randomization to second progression (PFS2)
• 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)
• 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)
• 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
• 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
• 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
• 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)
• Time to deterioration in pulmonary symptoms (TTFCD) [ Time Frame: Up to 5 years after last patient randomized ]
  Time to deterioration in pulmonary symptoms (TTFCD)
• 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
• 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-Blind

Primary Purpose: Treatment

• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Durvalumab
  Durvalumab IV (intravenous infusion)
• Drug: Oleclumab
  Oleclumab IV (intravenous infusion)
• Drug: Monalizumab
  Monalizumab IV (intravenous infusion)
• Other: Placebo
  Placebo IV (intravenous infusion)

Study Arms

• Experimental: Arm A: Durvalumab and Oleclumab
  Durvalumab on Day 1 of each 28-day cycle + Oleclumab on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months
  Interventions:

  • Drug: Durvalumab
  • Drug: Oleclumab
• Experimental: Arm B: Durvalumab and Monalizumab
  Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only
  Interventions:

  • Drug: Durvalumab
  • Drug: Monalizumab
  • Other: Placebo
• Active Comparator: Arm C: Durvalumab and Placebo
  Durvalumab on Day 1 of each 28-day cycle + Placebo on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months
  Interventions:

  • Drug: Durvalumab
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 11, 2022): 999
• Original Estimated Enrollment (submitted: February 2, 2022): 1000
• Estimated Study Completion Date: May 31, 2030
• Estimated Primary Completion Date: May 29, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

• Listed Location Countries: Australia, Brazil, Canada, China, Colombia, France, Germany, Italy, Japan, Korea, Republic of, Peru, Poland, Portugal, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam

Administrative Information

• NCT Number: NCT05221840
• Other Study ID Numbers: D9078C00001; 2023-503999-24-00 ( Registry Identifier: Clinical Trial Information System (CTIS) ); 2021-004346-37 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fabrice Barlesi, MD; Gustave Roussy, Cancer Campus, Grand Paris

• PRS Account: AstraZeneca
• Verification Date: April 2024