Durvalumab vs Placebo With Stereotactic Body Radiation Therapy in Early Stage Unresected Non-small Cell Lung Cancer Patients (PACIFIC-4)
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ClinicalTrials.gov Identifier: NCT03833154 |
Recruitment Status :
Recruiting
First Posted : February 6, 2019
Last Update Posted : February 21, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Carcinoma, Non-Small-Cell Lung | Drug: Durvalumab Other: Placebo Radiation: SBRT | Phase 3 |
Patients who are to receive SoC SBRT as definitive treatment of stage I-II lymph node-negative NSCLC and confirmed to meet all eligibility criteria will be randomized 1:1 to durvalumab or placebo.
The primary objective of this study is to assess the efficacy of durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS. Key secondary is to assess the efficacy of Durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of OS.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 706 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | Double- Blind |
Primary Purpose: | Treatment |
Official Title: | A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab With Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Patients With Unresected Stage I/II, Lymph-node Negative Non-small Cell Lung Cancer (PACIFIC-4/RTOG-3515) |
Actual Study Start Date : | March 6, 2019 |
Estimated Primary Completion Date : | June 28, 2024 |
Estimated Study Completion Date : | October 31, 2025 |

Arm | Intervention/treatment |
---|---|
Experimental: SoC SBRT + Durvalumab Therapy
SBRT - delivered in 3, 4, 5 or 8 fractions. Durvalumab (PD-L1 monoclonal antibody) 1500 mg every 4 weeks [q4w] intravenously [iv] for up to 24 months or until progression or other discontinuation criteria are met. |
Drug: Durvalumab
Durvalumab 1500 mg every 4 weeks [q4w] intravenously [iv] for up to 24 months or until progression or other discontinuation criteria are met.
Other Name: MEDI4736 Radiation: SBRT Delivered in 3, 4, 5 or 8 fractions. |
Placebo Comparator: SoC SBRT + Placebo Therapy
SBRT - delivered in 3, 4, 5 or 8 fractions. Placebo (matching placebo for infusion every 4 weeks iv for up to 24 months or until progression or other discontinuation criteria are met. |
Other: Placebo
Matching placebo for infusion every 4 weeks iv for up to 24 months or until progression or other discontinuation criteria are met. Radiation: SBRT Delivered in 3, 4, 5 or 8 fractions. |
- Progression-Free Survival (PFS) assessed by BICR according to RECIST 1.1 in subpopulation of patients with Stage I/II NSCLC [ Time Frame: up to 6 years ]
- Progression-Free Survival (PFS) assessed by BICR per RECIST 1.1 in all randomised patients with Stage I/II NSCLC [ Time Frame: up to 6 years ]
- Overall Survival (OS) [ Time Frame: up to 7 years ]
- Lung cancer-specific mortality [ Time Frame: up to 7 years ]
- Peak Plasma Concentration (Cmax) [ Time Frame: up to 27 months ]
- Detection of ADA neutralising antibodies titers [ Time Frame: up to 30 months ]
- Health-related quality of life in patients treated with durvalumab with SoC SBRT compared to placebo with SoC SBRT using the EORTC QLQ-C30 [ Time Frame: up to 7 years ]
- Proportion of patients alive and progression free at 24 months from randomisation (PFS24) assessed by BICR according to RECIST 1.1 [ Time Frame: at 24 months following randomization ]
- Time to progression (TTP) assessed by BICR according to RECIST 1.1 [ Time Frame: up to 6 years ]
- Time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1 [ Time Frame: up to 6 years ]
- Time from randomisation to second progression (PFS2) as defined by local standard clinical practice [ Time Frame: up to 7 years ]
- Trough Concentration (Ctrough) [ Time Frame: up to 27 months ]
- Assessment of AEs by CTCAE v 5.0 as measures of the safety and tolerability of durvalumab with SoC SBRT compared to placebo with SoC SBRT [ Time Frame: up to 27 months ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Age ≥18 years
- Histologically or cytologically documented Stage I to II NSCLC, with clinical Stage I/II lymph node-negative (T1 to T3N0M0) disease and planned to receive definitive treatment with SBRT. Patients may be medically inoperable or are medically operable and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as definitive therapy
- Planned SoC SBRT as definitive treatment
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) PS of 0, 1, or 2
- Life expectancy of at least 12 weeks
- Body weight >30 kg
- Submission of available tumor tissue sample
- Adequate organ and marrow function required
- Patients with central or peripheral lesions are eligible
- Staging studies must be done within 10 weeks before randomization
- Patients with a history of metachronus stage I/II (T1-T3N0M0) NSCLC treated definitively surgery only or SBRT only >1 year prior to enrollment are eligible.
Key Exclusion Criteria:
- Mixed small cell and non-small cell cancer
- History of allogeneic organ transplantation
- History of another primary malignancy with exceptions
- History of active primary immunodeficiency

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03833154
Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com | |
Contact: Astrazeneca Cancer Study Locator Service | 1-877-400-4656 | AstraZeneca@emergingmed.com |

Responsible Party: | AstraZeneca |
ClinicalTrials.gov Identifier: | NCT03833154 |
Other Study ID Numbers: |
D9103C00001 2018-002572-41 ( EudraCT Number ) |
First Posted: | February 6, 2019 Key Record Dates |
Last Update Posted: | February 21, 2021 |
Last Verified: | February 2021 |
Individual Participant Data (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 request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
Supporting Materials: |
Study Protocol 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 de-identified 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 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
NSCLC Double- Blind PD-L1 MEDI4736 Durvalumab PFS |
OS Unresected lung cancer Inoperable SBRT SABR |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases |
Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Durvalumab Antineoplastic Agents, Immunological Antineoplastic Agents |