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PACIFIC-9: A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05221840
Collaborator
(none)
999
Enrollment
186
Locations
3
Arms
99.7
Anticipated Duration (Months)
5.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
999 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, Double-blind, Placebo-controlled, Randomised, Multicentre, International Study of Durvalumab Plus Oleclumab and Durvalumab Plus Monalizumab in Patients With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Definitive, Platinum-Based Concurrent Chemoradiation Therapy
Actual Study Start Date :
Feb 7, 2022
Anticipated Primary Completion Date :
May 29, 2026
Anticipated Study Completion Date :
May 31, 2030

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A: Durvalumab and Oleclumab

Durvalumab on Day 1 of each 28-day cycle + Oleclumab on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months

Drug: Durvalumab
Durvalumab IV (intravenous infusion)

Drug: Oleclumab
Oleclumab IV (intravenous infusion)
Experimental: Arm B: Durvalumab and Monalizumab

Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only

Drug: Durvalumab
Durvalumab IV (intravenous infusion)

Drug: Monalizumab
Monalizumab IV (intravenous infusion)

Other: Placebo
Placebo IV (intravenous infusion)
Active Comparator: Arm C: Durvalumab and Placebo

Durvalumab on Day 1 of each 28-day cycle + Placebo on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months

Drug: Durvalumab
Durvalumab IV (intravenous infusion)

Other: Placebo
Placebo IV (intravenous infusion)

Outcome Measures

Primary Outcome Measures

  1. Progression Free Surival (PFS) [Up to 5 years after first patient randomized.]

    Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1.

Secondary Outcome Measures

  1. Overall Survival (OS) [Up to 9 years after first patient randomized]

    Overall survival (OS)

  2. Objective response rate (ORR) [Up to 5 years after first patient randomized]

    Objective response rate (ORR) per RECIST 1.1 as assessed by BICR

  3. Overall survival (OS) at 24 months [Up to 9 years after first patient randomized]

    Overall survival (OS) at 24 months

  4. Duration of response (DoR) [Up to 5 years after first patient randomized]

    Duration of response (DoR) per RECIST 1.1 as assessed by BICR

  5. Progression free survival (PFS) at 6, 12, 18, and 24 months [From date of randomization until 24 months]

    Progression free survival (PFS) at 6, 12, 18, and 24 months respectively, per RECIST 1.1 as assessed by BICR

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

    Time from randomization to second progression (PFS2)

  7. Time from randomization to first date of distant metastasis or death (TTDM) [Up to 5 years after first patient randomized]

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

  8. Time from randomization to start date of first subsequent therapy (TFST) [Up to 9 years after first patient randomized]

    Time from randomization to start date of first subsequent therapy (TFST)

  9. Progression free survival (PFS) as assessed by Investigator [Up to 5 years after first patient randomized]

    Progression free survival (PFS) as assessed by Investigator

  10. IHC analysis of PD-L1 TC expression [Up to 5 years after first patient randomized]

    IHC analysis of PD-L1 TC expression relative to efficacy outcomes

  11. Concentration of Durvalumab [From date of randomization until 3 months after date of last IP dose]

    To assess the Pharmacokinetics of Durvalumab when in combination with Monalizumab or Oleclumab - serum peak and trough concentrations

  12. Anti-drug antibodies (ADAs) [From date of randomization until 3 months after date of last IP dose]

    The immunogenicity of durvalumab, oleclumab, and monalizumab as assessed by presence of anti-drug antibodies (ADAs)

  13. Time to deterioration in pulmonary symptoms (TTFCD) [Up to 5 years after last patient randomized]

    Time to deterioration in pulmonary symptoms (TTFCD)

  14. Concentration of Oleclumab [From date of randomization until 3 months after last dose of IP]

    To assess the Pharmacokinetics of Oleclumab when in combination with Durvulumab - serum peak and trough concentrations

  15. Concentration of Monalizumab [From date of randomization until 3 months after last dose of IP]

    To assess the Pharmacokinetics of Monalizumab when in combination with Durvalumab - serum peak and trough concentrations

Eligibility Criteria

Criteria

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

  • Participant must be ≥ 18 years at the time of screening.

  • Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease

  • Provision of a tumour tissue sample obtained prior to CRT

  • Documented tumour PD-L1 status by central lab

  • Documented EGFR and ALK wild-type status (local or central).

  • Patients must not have progressed following definitive, platinum based, concurrent chemoradiotherapy

  • Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy,

  • 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.

  • WHO performance status of 0 or 1 at randomization

  • Adequate organ and marrow function

EXCLUSION CRITERIA:

  • 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.

  • Mixed small cell and non-small cell lung cancer histology.

  • Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.

  • Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.

  • Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia).

  • Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.

  • 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.

  • Active or prior documented autoimmune or inflammatory disorders (with exceptions)

  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site San Diego California United States 92123
2 Research Site New Haven Connecticut United States 06510
3 Research Site Urbana Illinois United States 61801
4 Research Site Waterloo Iowa United States 50703
5 Research Site Lexington Kentucky United States 40503
6 Research Site Scarborough Maine United States 04074
7 Research Site Baltimore Maryland United States 21201
8 Research Site Grand Rapids Michigan United States 49503
9 Research Site Duluth Minnesota United States 55805
10 Research Site Duluth Minnesota United States 55812
11 Research Site Billings Montana United States 59101
12 Research Site Ridgewood New Jersey United States 07450
13 Research Site Greensboro North Carolina United States 27403
14 Research Site Portland Oregon United States 97239
15 Research Site Philadelphia Pennsylvania United States 19104
16 Research Site Sioux Falls South Dakota United States 57105
17 Research Site Charlottesville Virginia United States 22908
18 Research Site Fairfax Virginia United States 22031
19 Research Site Richmond Virginia United States 23235
20 Research Site Richland Washington United States 99352
21 Research Site Spokane Washington United States 99204
22 Research Site Tacoma Washington United States 98405
23 Research Site Milwaukee Wisconsin United States 53226
24 Research Site Box Hill Australia 3128
25 Research Site East Melbourne Australia 3002
26 Research Site Elizabeth Vale Australia 5112
27 Research Site Gosford Australia 2250
28 Research Site Heidelberg Australia 3084
29 Research Site South Brisbane Australia 4101
30 Research Site St Albans Australia 3021
31 Research Site St. Leonards Australia 2065
32 Research Site Westmead Australia 2145
33 Research Site Belo Horizonte Brazil 30380-090
34 Research Site Florianópolis Brazil 88034-000
35 Research Site Jaú Brazil 17210-120
36 Research Site Porto Alegre Brazil 90610-000
37 Research Site Porto Alegre Brazil 91350-200
38 Research Site Recife Brazil 52010-075
39 Research Site Sao Paulo Brazil 01323-903
40 Research Site Uberlândia Brazil 38408-150
41 Research Site Vitoria Brazil 29043-260
42 Research Site Edmonton Alberta Canada T6G 1Z2
43 Research Site Hamilton Ontario Canada L8V 5C2
44 Research Site Kingston Ontario Canada K7L 2V7
45 Research Site London Ontario Canada N6A 5W9
46 Research Site Toronto Ontario Canada M5G 2M9
47 Research Site Anyang China 455000
48 Research Site Beijing China 100021
49 Research Site Beijing China
50 Research Site Changchun China 130021
51 Research Site Changsha China 410008
52 Research Site Changsha China 410013
53 Research Site Guangzhou China 510060
54 Research Site Guangzhou China 510062
55 Research Site Hangzhou China 310002
56 Research Site Hangzhou China 310022
57 Research Site Hefei China 133500
58 Research Site Hefei China 230031
59 Research Site Kunming China 650118
60 Research Site Linhai China 317000
61 Research Site Nanchang China 330006
62 Research Site Nanning China 530021
63 Research Site Nantong China 226361
64 Research Site Neijiang China 641000
65 Research Site Ningbo China 315100
66 Research Site Shanghai China 200433
67 Research Site Shaoguan China 512027
68 Research Site Shenyang China 110042
69 Research Site Tianjin China 300060
70 Research Site Wuhan China 430022
71 Research Site Wuhan China 430071
72 Research Site Wuhan China 430079
73 Research Site Zhanjiang China 524001
74 Research Site Zhengzhou City China 450000
75 Research Site Zhengzhou China 450008
76 Research Site Zhongshan China 528403
77 Research Site Zhuhai China 519000
78 Research Site Barranquilla Colombia 080012
79 Research Site Barranquilla Colombia 080020
80 Research Site Bogotá Colombia
81 Research Site Medellin Colombia 050034
82 Research Site Valledupar Colombia 200001
83 Research Site Bordeaux France 33075
84 Research Site Creteil Cedex France 94010
85 Research Site Montpellier France 34298
86 Research Site Rouen France 76031
87 Research Site Villejuif Cedex France 94805
88 Research Site Erfurt Germany 99089
89 Research Site Erlangen Germany 91054
90 Research Site Esslingen Germany 73730
91 Research Site Guetersloh Germany 33332
92 Research Site Hannover Germany 30459
93 Research Site Oldenburg Germany 26121
94 Research Site Brescia Italy 25123
95 Research Site Firenze Italy 50134
96 Research Site Meldola Italy 47014
97 Research Site Parma Italy 43126
98 Research Site Pavia Italy 27100
99 Research Site Roma Italy 00128
100 Research Site Himeji-shi Japan 670-8520
101 Research Site Hiroshima-shi Japan 730-0011
102 Research Site Kashiwa Japan 227-8577
103 Research Site Kurume-shi Japan 830-0011
104 Research Site Natori-shi Japan 981-1293
105 Research Site Niigata-shi Japan 951-8566
106 Research Site Osaka-shi Japan 541-8567
107 Research Site Sendai-shi Japan 980-0873
108 Research Site Tokushima-shi Japan 770-8503
109 Research Site Toon-shi Japan 791-0295
110 Research Site Wakayama-shi Japan 641-8510
111 Research Site Changwon-si Korea, Republic of 51353
112 Research Site Cheongju-si Korea, Republic of 28644
113 Research Site Seongnam-si Korea, Republic of 13620
114 Research Site Seoul Korea, Republic of 03080
115 Research Site Seoul Korea, Republic of 03722
116 Research Site Seoul Korea, Republic of 05505
117 Research Site Suwon-si Korea, Republic of 16499
118 Research Site Suwon Korea, Republic of 16247
119 Research Site Concepción Peru 12125
120 Research Site Lima Peru 15036
121 Research Site Lima Peru LIMA 11
122 Research Site Lima Peru LIMA 29
123 Research Site Lima Peru Lima 34
124 Research Site Trujillo Peru
125 Research Site Brzozów Poland 36-200
126 Research Site Bydgoszcz Poland 85-796
127 Research Site Koszalin Poland 75-581
128 Research Site Siedlce Poland 08-110
129 Research Site Tomaszów Mazowiecki Poland 97-200
130 Research Site Warszawa Poland 02-781
131 Research Site Lisboa Portugal 1400-048
132 Research Site Lisboa Portugal 1769-001
133 Research Site Lisboa Portugal 1998-018
134 Research Site Loures Portugal 2674-514
135 Research Site Porto Portugal 4200-319
136 Research Site Barcelona Spain 08035
137 Research Site Barcelona Spain 8003
138 Research Site Granada Spain 18016
139 Research Site Madrid Spain 28034
140 Research Site Madrid Spain 28040
141 Research Site Santiago de Compostela Spain 15706
142 Research Site Valencia Spain 46010
143 Research Site Hsinchu Taiwan 300
144 Research Site Taichung Taiwan 402
145 Research Site Taichung Taiwan 40705
146 Research Site Taipei 112 Taiwan
147 Research Site Taipei Taiwan 100
148 Research Site Taipei Taiwan 11490
149 Research Site Taipei Taiwan 23561
150 Research Site Taoyuan City Taiwan 333
151 Research Site Bangkok Thailand 10300
152 Research Site Bangkok Thailand 10700
153 Research Site Chonburi Thailand 20000
154 Research Site Hat Yai Thailand 90110
155 Research Site Khon Kaen Thailand 40000
156 Research Site Khon Kaen Thailand 40002
157 Research Site Lampang Thailand 52000
158 Research Site Muang Thailand 22000
159 Research Site Muang Thailand 50200
160 Research Site Naimuang Thailand 30000
161 Research Site Ankara Turkey 06010
162 Research Site Ankara Turkey 06230
163 Research Site Ankara Turkey 06800
164 Research Site Diyarbakir Turkey 21280
165 Research Site Goztepe Istanbul Turkey
166 Research Site Karsiyaka Turkey 35575
167 Research Site Chernihiv Ukraine 14029
168 Research Site Kharkiv Region Ukraine 61018
169 Research Site Kropyvnytskyi Ukraine 25011
170 Research Site Kyiv Ukraine 03680
171 Research Site Uzhgorod Ukraine 88000
172 Research Site Zaporizhzhia Ukraine 69000
173 Research Site Belfast United Kingdom BT9 7AB
174 Research Site Bristol United Kingdom BS2 8ED
175 Research Site Dundee United Kingdom DD1 9SY
176 Research Site Edinburgh United Kingdom EH4 2XR
177 Research Site Hampshire United Kingdom SO16 6YD
178 Research Site London United Kingdom NW1 2PG
179 Research Site Middlesbrough United Kingdom TS4 3BW
180 Research Site Poole United Kingdom BH15 2JB
181 Research Site Rhyl United Kingdom LL18 5UJ
182 Research Site Torquay United Kingdom TQ2 7AA
183 Research Site Truro United Kingdom TR1 3LJ
184 Research Site Wolverhampton United Kingdom WV10 OQP
185 Research Site Hanoi Vietnam 100000
186 Research Site Ho Chi Minh city Vietnam 700000

Sponsors and Collaborators

  • AstraZeneca

Investigators

  • Principal Investigator: Fabrice Barlesi, MD, Gustave Roussy, Cancer Campus, Grand Paris

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT05221840
Other Study ID Numbers:
  • D9078C00001
  • 2021-004346-37
First Posted:
Feb 3, 2022
Last Update Posted:
Jul 25, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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 Jul 25, 2022