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

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: Domvanalimab; Drug: Durvalumab; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05211895

2021-004327-32 (EudraCT Number)

D9075C00001

Details and patient eligibility

About

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.

Enrollment: 860 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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:

   • 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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860 participants in 2 patient groups

Arm A: Durvalumab + Domvanalimab

Experimental group

Description:

Durvalumab and domvanalimab as an IV infusion q4w, starting on Day 1 for up to a maximum of 12 months

Treatment:

Drug: Durvalumab

Drug: Domvanalimab

Arm B: Durvalumab + Placebo

Active Comparator group

Description:

Durvalumab + placebo as an IV infusion q4w starting on Day 1 for up to a maximum of 12 months

Treatment:

Other: Placebo

Drug: Durvalumab