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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05211895
• Collaborator: Arcus Biosciences, Inc. (Industry)
• Enrollment: 860
• Locations: 129
• Arms: 2
• Anticipated Duration (Months): 91.3
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Durvalumab; Drug: Domvanalimab; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 860 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, 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
• Actual Study Start Date: Feb 18, 2022
• Anticipated Primary Completion Date: Jun 2, 2027
• Anticipated Study Completion Date: Sep 28, 2029

Arms and Interventions

Arm	Intervention/Treatment
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	Drug: Durvalumab; Durvalumab IV (Intravenous infusion); Drug: Domvanalimab; Domvanalimab IV (Intravenous infusion)
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	Drug: Durvalumab; Durvalumab IV (Intravenous infusion); Other: Placebo; Placebo IV (Intravenous infusion)

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [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%.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [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%

2. Overall Survival (OS) [Approximately 8 years after first patient randomized]

   Overall Survival (OS)

3. Objective Response Rate (ORR) [Approximately 8 years after first patient randomized]

   Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR

4. Duration of Response (DoR) [Approximately 8 years after first patient randomized]

   Duration of Response (DoR) using BICR assessment according to RECIST 1.1

5. Time from randomization to second progression (PFS2) [Approximately 8 years after first patient randomized]

   Time from randomization to second progression (PFS2)

6. Time from randomization to first date of distant metastasis or death (TTDM) [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).

7. Time to first subsequent therapy (TFST) [Approximately 8 years after first patient randomized]

   Time to first subsequent therapy (TFST)

8. Concentration of Durvalumab and Domvanalimab [Approximately 12 weeks after last IP dose]

   The pharmacokinetics (PK) of Durvalumab and Domvanalimab as determined by concentration

9. PFS6, PFS12, PFS18, PFS24 [Approximately 6, 12, 18 and 24 months after last patient randomized]

   PFS at 6, 12, 18 and 24 months (proportion per Kaplan-Meier)

10. Anti-Drug Antibodies (ADAs) [Approximately 12 weeks after last IP dose.]

    The immunogenicity of Durvalumab and domvanalimab as assessed by presence of Anti-Drug Antibodies (ADAs)

11. Time to deterioration in pulmonary symptoms (TTFCD) [Approximately 8 years after first patient randomized]

    Time to deterioration in pulmonary symptoms (TTFCD)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy, 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, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, ILD, pleural effusion, or pulmonary fibrosis diagnosed in the past 6 months prior to randomization.

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.

Reproduction

1. Negative pregnancy test (serum) for WOCBP:

2. Female participants must be 1 year post menopausal, surgically sterile, or using 1 highly effective form of birth control

3. Male participants who intend to be sexually active with a WOCBP must be surgically sterile or using an acceptable method of contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Mesa	Arizona	United States	85206
2	Research Site	Phoenix	Arizona	United States	85054
3	Research Site	Santa Rosa	California	United States	95403
4	Research Site	Orlando	Florida	United States	32804
5	Research Site	Macon	Georgia	United States	31217
6	Research Site	Maywood	Illinois	United States	60153
7	Research Site	Louisville	Kentucky	United States	40202
8	Research Site	Baltimore	Maryland	United States	21224
9	Research Site	Silver Spring	Maryland	United States	20910
10	Research Site	Detroit	Michigan	United States	48202
11	Research Site	Minneapolis	Minnesota	United States	55407
12	Research Site	Florham Park	New Jersey	United States	07932
13	Research Site	Buffalo	New York	United States	14203
14	Research Site	Charlotte	North Carolina	United States	28203
15	Research Site	Winston-Salem	North Carolina	United States	27157
16	Research Site	Fort Sam Houston	Texas	United States	78234
17	Research Site	Arlington	Virginia	United States	22205
18	Research Site	Fort Belvoir	Virginia	United States	22060
19	Research Site	Brussels		Belgium	1160
20	Research Site	Edegem		Belgium	2650
21	Research Site	Haine-Saint-Paul		Belgium	7100
22	Research Site	Leuven		Belgium	3000
23	Research Site	Liege		Belgium	4000
24	Research Site	Sint-Niklaas		Belgium	9100
25	Research Site	Las Condes		Chile	7560908
26	Research Site	Puerto Montt		Chile	5500243
27	Research Site	Santiago		Chile	7500713
28	Research Site	Santiago		Chile	7630370
29	Research Site	Santiago		Chile	8241479
30	Research Site	Temuco		Chile	4810218
31	Research Site	Baotou		China	140400
32	Research Site	Beijing		China	100142
33	Research Site	Chengdu		China	610041
34	Research Site	Chongqing		China	400037
35	Research Site	Hangzhou		China	310020
36	Research Site	Shandong		China
37	Research Site	Shenzhen		China	518036
38	Research Site	Berlin-Zehlendorf		Germany	14165
39	Research Site	Berlin		Germany	12351
40	Research Site	Georgsmarienhuette		Germany	49124
41	Research Site	Halle		Germany	06120
42	Research Site	Hamburg		Germany	21075
43	Research Site	Homburg		Germany	66421
44	Research Site	Koblenz		Germany	56073
45	Research Site	Moers		Germany	47441
46	Research Site	München		Germany	81675
47	Research Site	Regensburg		Germany	93049
48	Research Site	Athens		Greece	11526
49	Research Site	Athens		Greece	11527
50	Research Site	Athens		Greece	12462
51	Research Site	Holargos, Athens		Greece	155 62
52	Research Site	Budapest		Hungary	1121
53	Research Site	Budapest		Hungary	1122
54	Research Site	Deszk		Hungary	6772
55	Research Site	Győr		Hungary	9024
56	Research Site	Székesfehérvár		Hungary	8000
57	Research Site	Törökbálint		Hungary	2045
58	Research Site	Bangalore		India	560064
59	Research Site	Kolkata		India	700160
60	Research Site	Marg Jaipur		India	302004
61	Research Site	Rohini		India	110 085
62	Research Site	Fukuoka-shi		Japan	812-8582
63	Research Site	Hidaka-shi		Japan	350-1298
64	Research Site	Koto-ku		Japan	135-8550
65	Research Site	Matsuyama-shi		Japan	791-0280
66	Research Site	Nagoya-shi		Japan	464-8681
67	Research Site	Sunto-gun		Japan	411-8777
68	Research Site	Tokyo		Japan	104-0045
69	Research Site	Yokohama-shi		Japan	241-8515
70	Research Site	Daegu		Korea, Republic of	42415
71	Research Site	Goyang-si		Korea, Republic of	10408
72	Research Site	Gyeongsangnam-do		Korea, Republic of	52727
73	Research Site	Incheon		Korea, Republic of	21431
74	Research Site	Seoul		Korea, Republic of	02841
75	Research Site	Seoul		Korea, Republic of	06273
76	Research Site	Seoul		Korea, Republic of	06351
77	Research Site	Seoul		Korea, Republic of	07061
78	Research Site	Johor Bahru		Malaysia	81100
79	Research Site	Kuala Lumpur		Malaysia	59100
80	Research Site	Kuala Lumpur		Malaysia	59100
81	Research Site	Kuching		Malaysia	93586
82	Research Site	Selangor		Malaysia	46050
83	Research Site	Oslo		Norway	0450
84	Research Site	Trondheim		Norway	0730
85	Research Site	Iloilo City		Philippines	5000
86	Research Site	Muntinlupa City		Philippines	1780
87	Research Site	Quezon City		Philippines	1100
88	Research Site	Quezon City		Philippines	1112
89	Research Site	Barnaul		Russian Federation	656049
90	Research Site	Kazan		Russian Federation	420029
91	Research Site	Moscow		Russian Federation	121205
92	Research Site	Moscow		Russian Federation	129090
93	Research Site	Nizhny Novgorod		Russian Federation	603126
94	Research Site	Novosibirsk		Russian Federation	630099
95	Research Site	Perm		Russian Federation	614990
96	Research Site	Saint Petersburg		Russian Federation	196006
97	Research Site	Tomsk		Russian Federation	634028
98	Research Site	Amanzimtoti		South Africa	4126
99	Research Site	Amanzimtoti		South Africa	4126
100	Research Site	Cape Town		South Africa	7570
101	Research Site	Johannesburg		South Africa	2196
102	Research Site	Parktown		South Africa	2193
103	Research Site	Pretoria		South Africa	0084
104	Research Site	Bilbao (Vizcaya)		Spain	48013
105	Research Site	Castello de la Plana		Spain	12002
106	Research Site	Cordoba		Spain	14004
107	Research Site	El Palmar		Spain	30120
108	Research Site	Palma de Mallorca		Spain	07010
109	Research Site	Sabadell (Barcelona)		Spain	08208
110	Research Site	Hsinchu		Taiwan	300
111	Research Site	New-Taipei		Taiwan	220216
112	Research Site	Taichung		Taiwan	40705
113	Research Site	Tainan		Taiwan
114	Research Site	Taipei		Taiwan	10002
115	Research Site	Taipei		Taiwan	10449
116	Research Site	Taipei		Taiwan	11217
117	Research Site	Taoyuan		Taiwan	333
118	Research Site	Adapazari		Turkey	54290
119	Research Site	Ankara		Turkey	06340
120	Research Site	Ankara		Turkey	6100
121	Research Site	Antalya		Turkey	07058
122	Research Site	Edirne		Turkey	22030
123	Research Site	Istanbul		Turkey	34098
124	Research Site	Istanbul		Turkey	34662
125	Research Site	Izmir		Turkey	35360
126	Research Site	Konya		Turkey	42080
127	Research Site	Çankaya		Turkey	06680
128	Research Site	Birmingham		United Kingdom	B9 5SS
129	Research Site	Leeds		United Kingdom	LS 9 7TF

Sponsors and Collaborators

• AstraZeneca
• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05211895
• Other Study ID Numbers: D9075C00001; 2021-004327-32
• First Posted: Jan 27, 2022
• Last Update Posted: Aug 11, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: non-small cell lung cancer; locally advanced; NSCLC
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Durvalumab

Study Results

No Results Posted as of Aug 11, 2022