A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC (PACIFIC-8)

• ClinicalTrials.gov Identifier: NCT05211895
• Recruitment Status: Recruiting
• First Posted: January 27, 2022
• Last Update Posted: April 19, 2024
• Sponsor: AstraZeneca
• Collaborator: Arcus Biosciences, Inc.
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: January 11, 2022
• First Posted Date: January 27, 2022
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: February 18, 2022
• Estimated Primary Completion Date: June 27, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 26, 2022)

Progression Free Survival (PFS) [ Time Frame: Up to 8 years after first patient randomised ]

Defined as time from randomisation until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause in participants with PD-L1 TC ≥ 50%.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 14, 2022)

• Progression Free Survival (PFS) [ Time Frame: Up to 8 years after first patient randomised ]
  Defined as time from randomisation until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause in participants with PD-L1 TC ≥ 1%
• Overall Survival (OS) [ Time Frame: Approximately 8 years after first patient randomized ]
  Overall Survival (OS)
• Objective Response Rate (ORR) [ Time Frame: Approximately 8 years after first patient randomized ]
  Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR
• Duration of Response (DoR) [ Time Frame: Approximately 8 years after first patient randomized ]
  Duration of Response (DoR) using BICR assessment according to RECIST 1.1
• Time from randomization to second progression (PFS2) [ Time Frame: Approximately 8 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: Approximately 8 years after first patient randomized ]
  Time from randomization until the first date of distant metastasis or death in the absence of distant metastasis (TTDM).
• Time to first subsequent therapy (TFST) [ Time Frame: Approximately 8 years after first patient randomized ]
  Time to first subsequent therapy (TFST)
• Concentration of Durvalumab and Domvanalimab [ Time Frame: Approximately 12 weeks after last IP dose ]
  The pharmacokinetics (PK) of Durvalumab and Domvanalimab as determined by concentration
• PFS6, PFS12, PFS18, PFS24 [ Time Frame: Approximately 6, 12, 18 and 24 months after last patient randomized ]
  PFS at 6, 12, 18 and 24 months (proportion per Kaplan-Meier)
• Anti-Drug Antibodies (ADAs) [ Time Frame: Approximately 12 weeks after last IP dose. ]
  The immunogenicity of Durvalumab and domvanalimab as assessed by presence of Anti-Drug Antibodies (ADAs)
• Time to deterioration in pulmonary symptoms (TTFCD) [ Time Frame: Approximately 8 years after first patient randomized ]
  Time to deterioration in pulmonary symptoms (TTFCD)

Original Secondary Outcome Measures (submitted: January 26, 2022)

• Overall Survival (OS) [ Time Frame: Approximately 8 years after first patient randomized ]
  Overall Survival (OS)
• Objective Response Rate (ORR) [ Time Frame: Approximately 8 years after first patient randomized ]
  Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR
• Duration of Response (DoR) [ Time Frame: Approximately 8 years after first patient randomized ]
  Duration of Response (DoR) using BICR assessment according to RECIST 1.1
• Time from randomization to second progression (PFS2) [ Time Frame: Approximately 8 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: Approximately 8 years after first patient randomized ]
  Time from randomization until the first date of distant metastasis or death in the absence of distant metastasis (TTDM).
• Time to first subsequent therapy (TFST) [ Time Frame: Approximately 8 years after first patient randomized ]
  Time to first subsequent therapy (TFST)
• Concentration of Durvalumab and Domvanalimab [ Time Frame: Approximately 12 weeks after last IP dose ]
  The pharmacokinetics (PK) of Durvalumab and Domvanalimab as determined by concentration
• PFS6, PFS12, PFS18, PFS24 [ Time Frame: Approximately 6, 12, 18 and 24 months after last patient randomized ]
  PFS at 6, 12, 18 and 24 months (proportion per Kaplan-Meier)
• Anti-Drug Antibodies (ADAs) [ Time Frame: Approximately 12 weeks after last IP dose. ]
  The immunogenicity of Durvalumab and domvanalimab as assessed by presence of Anti-Drug Antibodies (ADAs)
• Time to deterioration in pulmonary symptoms (TTFCD) [ Time Frame: Approximately 8 years after first patient randomized ]
  Time to deterioration in pulmonary symptoms (TTFCD)

• 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 + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC
• Official Title: A Phase III, Randomised, Double-blind, Placebo-controlled, Multicentre, International Study of Durvalumab Plus Domvanalimab(AB154) in Participants With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer Whose Disease Has Not Progressed Following Definitive Platinum-based Concurrent Chemoradiation Therapy
• Brief Summary: This is a Phase III, randomised, double-blind, placebo-controlled, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) and domvanalimab (AB154) compared with durvalumab plus placebo in adults with locally advanced (Stage III), unresectable NSCLC whose disease has not progressed following definitive 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: Domvanalimab
  Domvanalimab IV (Intravenous infusion)
• Other: Placebo
  Placebo IV (Intravenous infusion)

Study Arms

• Experimental: Arm A: Durvalumab + Domvanalimab
  Durvalumab and domvanalimab as an IV infusion q4w, starting on Day 1 for up to a maximum of 12 months
  Interventions:

  • Drug: Durvalumab
  • Drug: Domvanalimab
• Active Comparator: Arm B: Durvalumab + Placebo
  Durvalumab + placebo as an IV infusion q4w starting on Day 1 for up to a maximum of 12 months
  Interventions:

  • Drug: Durvalumab
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 26, 2022): 860
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 30, 2030
• Estimated Primary Completion Date: June 27, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA:

1. Participant must be ≥ 18 years at the time of screening.
2. Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
3. Provision of a tumour tissue sample obtained prior to CRT
4. Documented tumour PD-L1 status ≥ 1% by central lab
5. Documented EGFR and ALK wild-type status (local or central).
6. Patients must not have progressed following definitive, platinum-based, concurrent chemoradiotherapy
7. Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
8. 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.
9. WHO performance status of 0 or 1 at randomization
10. Adequate organ and marrow function

EXCLUSION CRITERIA:

1. 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. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours treated with curative intent and without evidence of disease.
2. Mixed small cell and non-small cell lung cancer histology.
3. Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
4. Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
5. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia).
6. Participants with ≥ grade 2 pneumonitis from prior chemoradiation therapy.
7. 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
8. Active or prior documented autoimmune or inflammatory disorders (with exceptions)
9. Active EBV infection, or known or suspected chronic active EBV infection at screening
10. 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: Belgium, Brazil, Canada, Chile, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Norway, Philippines, Poland, Romania, South Africa, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: China, Russian Federation

Administrative Information

• NCT Number: NCT05211895
• Other Study ID Numbers: D9075C00001; 2021-004327-32 ( 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: Not Provided
• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Arcus Biosciences, Inc.

Investigators

• Principal Investigator: Hidehito Horinouchi, MD, PhD; National Cancer Center Hospital
• Principal Investigator: Alexander Spira, MD, PhD; Virginia Cancer Specialists Research Institute
• Principal Investigator: Jinming Yu, MD, PhD; Shandong Cancer Hospital and Institute

• PRS Account: AstraZeneca
• Verification Date: April 2024