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 (PACIFIC-9)
- Conditions
- C349 Bronchus or lung, unspecifiedBronchus or lung, unspecifiedC349
- Registration Number
- PER-008-22
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Without startig enrollment
- Sex
- All
- Target Recruitment
- 0
Part II Screening
Participants may enter part II screening even if the results of the Part I screening procedures are still pending.
Participants are eligible to be randomised to the study only if all of the following Part II inclusion criteria and none of the exclusion criteria apply:
Type of Participant and Disease Characteristics
1Patients must not have progressed following definitive, platinum-based, cCRT as demonstrated by the following imaging studies performed after completion of CRT:
(a)Screening baseline RECIST 1.1 imaging of chest and abdomen by CT (preferred) or MRI (see schedule of assessments Table 1)
(b) Brain MRI (preferred) or high-quality CT with IV contrast (See schedule of assessments Table 1).
2Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy, which must be completed within 1 to 28 days prior to first dose of investigational product in the study (one chemotherapy cycle is defined as 21 or as 28 days). Sites are strongly encouraged to complete screening within the first 14 days of the 28-day screening period.
3The platinum-based chemotherapy regimen must be cisplatin or carboplatin-based and contain one of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel or docetaxel), or pemetrexed, according to the local standard of care regimens. Gemcitabine is not permitted.
4The last dose of chemotherapy must be administered prior to, or concurrently with, the final dose of radiation. Consolidation chemotherapy after radiation is not permitted. Up to 2 cycles of induction chemotherapy prior to cCRT is permitted.
5Where possible, chemotherapy regimens should be given according to National Comprehensive Cancer Network (NCCN) Guidelines or European Society for Medical Oncology (ESMO) Guidelines.
6Participants 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. Sites are encouraged to adhere to the following organ dosimetric specifications:
-Mean lung dose must be <20 Gy and/or V20 must be <35%
-Mean eosophagus dose must be <34 Gy
-Heart V45 <35% or V30 <50%.
7Minimum life expectancy of 12 weeks at randomization
8WHO performance status of 0 or 1 at randomization
9Adequate organ and marrow function as defined below:
-Absolute neutrophil count > 1.5 x 109/L (1500 per mm3)
-Platelets > 75 x 109/L (75000 per mm3)
-Haemoglobin = 9.0 g/dL (5.59 mmol/L)
-Serum creatinine CL >40 mL/min by the Cockcroft-Gault formula
or by 24-hour urine collection for determination of creatinine clearance:
Males:
Creatinine CL (mL/min)=Weight (kg) x (140 – Age)
72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min)=Weight (kg) x (140 – Age)x 0.85
72 x serum creatinine (mg/dL)
-Serum bilirubin =1.5 x upper limit of normal (ULN) or < 3 x ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia).
-AST and ALT =2.5 x ULN.
Weight
10Minimum body weight = 40kg at enrolment and randomization.
Reproduction
11Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
12Negative pregnancy test (serum) for women o
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diseases, active infection, active interstitial lung disease/pneumonitis, serious chronic gastrointestinal conditions associated with diarrhoea, psychiatric illness/social situations) which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol
2History 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.
3Mixed small cell and non-small cell lung cancer histology.
4Participants who have had disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumours
5Participants with T4 lesions that invade major vascular structures such as pulmonary artery or cardiac tissues are not eligible.
6Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
7Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
8Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia). Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss) after consultation with the AstraZeneca study clinical lead.
9Participants with =grade 2 pneumonitis from prior chemoradiation therapy.
10Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
11History 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.
12Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, autoimmune pneumonitis and autoimmune myocarditis, etc). The following are exceptions to this criterion:
•Participants with vitiligo or alopecia.
•Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
•Any chronic skin condition that does not require systemic therapy.
•Participants without active disease in the last 5 years may be included but only after consultation with the study clinical lead.
•Participants with coeliac disease controlled by diet alone.
13Active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method