A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC 8)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 May 2022 → ongoing

Decision date (initial)

2024-02-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-506891-28-00

EudraCT number

2021-004327-32

ClinicalTrials.gov

NCT05211895

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with locally advanced, unresectable NSCLC who have not progressed on prior platinum-basedcCRT, with PD-L1 TC ≥ 50%, progression free survival (PFS) assessed by Blinded Independent Central Review (BICR).

Secondary objectives 1

1. To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with TC ≥ 1%, progression free survival (PFS) assessed by Blinded Independent Central Review (BICR). To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with TC ≥ 1% or TC ≥ 50% in the following outcomes: •Overall response rate (ORR) •Duration of response (DoR) •Time to second progression (PFS2) •Time to death or distant metastatis (TTDM) •Time to First Subsequent Therapy (TFST) •PFS at 6, 12, 18 and 24 months •Overall Survival at 24 months (OS 24) •Overall Survival (OS) •PFS as assessed by investigator •Time to deterioration in pulmonary symptoms PK and immunogenicity of durvalumab and domvanalimab To assess the safety and tolerability of durvalumab plus domvanalimab as compared to durvalumab plus placebo.

Conditions and MedDRA coding

The target population of interest in this study is participants with locally advanced (Stage III), unresectable NSCLC, whose tumours express PD L1 TC ≥ 1% as assessed by a central reference laboratory using the VENTANA PD-L1 (SP263) IHC assay, and who did not progress after definitive platinum based cCRT.

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 tumor tissue sample obtained prior to CRT. 4. Documented tumor 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

1. 1. History of another primary malignancy, except for: -Malignancies treated with curative intent and adequate follow-up with no known active disease and have not required active treatment within the past 3 years before the first dose of study intervention and of low potential risk of recurrence. -Adequately resected non melanoma skin cancer or lentigo maligna without evidence of disease. -Adequately treated carcinoma in situ, including Ta tumors 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS) using Blinded Independent Central Review (BICR) assessment according to RECIST 1.1 with participants with PD-L1 TC>=50%. PFS will be evaluated every 00 weeks (±00 days) from randomisation through 00 weeks, and q00w (± 00 days) thereafter until RECIST 1.1 defined radiological progression, plus 1 or more follow-up scans.

Secondary endpoints 1

1. PFS in PD-L1 TC ≥ 1% by BICR. Comparison of durvalumab + domvanalimab to durvalumab + placebo in TC ≥ 1% or TC ≥ 50% in: 1. Overall Survival (OS) 2. PFS by investigator 3. PFS6, PFS12, PFS18, PFS24 4. OS at 24 months 5. ORR and DoR by BICR 6. PFS2, TTDM, TFST 7. PK and immunogenicity of durvalumab and domvanalimab 8. Time to First Confirmed Deterioration (TTFCD) in pulmonary symptoms measured by the NSCLC-SAQ.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

10 EU/EEA countries · 81 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 130 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications