C349 Bronchus or lung, unspecified Bronchus or lung, unspecified
Conditions
Interventions
Durvalumab 1500 mg on Day 1 of each 28-day cycle + oleclumab 3000 mg 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. - Durvalumab 1500 mg + monal
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 1 Patients 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). 2 Participants 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. 3 The 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. 4 The 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. 5 Where possible, chemotherapy regimens should be given according to National Comprehensive Cancer Network (NCCN) Guidelines or European Society for Medical Oncology (ESMO) Guidelines. 6 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. Sites are encouraged to adhere to the following organ dosimetric specifications: - Mean lung dose must be 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 10 Minimum body weight = 40kg at enrolment and randomization. Reproduction 11 Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 12 Negative pregnancy test (serum) for women of childbearing potential. 13 Female participants must be 1 year post-menopausal, surgically sterile, or using one hig
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1 As 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 2 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. 3 Mixed small cell and non-small cell lung cancer histology. 4 Participants who have had disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumours 5 Participants with T4 lesions that invade major vascular structures such as pulmonary artery or cardiac tissues are not eligible. 6 Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC. 7 Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT. 8 Any 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. 9 Participants with =grade 2 pneumonitis from prior chemoradiation therapy. 10 Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1. 11 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. 12 Active 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. 13 Active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HB
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. ? PFS will be measured by HR. ? The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anticancer therapy, or clinically progresses prior to RECIST 1.1 progression. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits NAME OF THE RESULT: superiority of durvalumab + oleclumab relative to durvalumab + placebo in participants with unresectable, Stage III NSCLC who have not progressed on prior platinum-based cCRT PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study;PFS as defined above NAME OF THE RESULT: To demonstrate superiority of durvalumab + monalizumab relative to durvalumab + placebo in participants with unresectable, Stage III NSCLC who have not progressed on prior platinum-based cCRT ? Assessment by PFS as assessed by BICR. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study | — |
Secondary
| Measure | Time frame |
|---|---|
| ? Time to first confirmed deterioration (TTFCD) of cough, dyspnoea, and chest pain (single-item scores) as measured by the NSCLC-SAQ. ? TTFCD as measured by HR. NAME OF THE RESULT: To assess time to deterioration in pulmonary symptoms (cough, dyspnoea, chest pain) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study;PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. ? PFS will be measured by HR. ? The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anticancer therapy, or clinically progresses prior to RECIST 1.1 progression. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits NAME OF THE RESULT: superiority of durvalumab + oleclumab relative to durvalumab + placebo in participants with unresectable, Stage III NSCLC who have not progressed on prior platinum-based cCRT PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study;PFS as defined above NAME OF THE RESULT: To demonstrate superiority of durvalumab + monalizumab relative to durvalumab + placebo in participants with unresectable, Stage III NSCLC who have not progressed on prior platinum-based cCRT ? Assessment by PFS as assessed by BICR. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study;OS is defined as time from randomization until the date of death due to any cause. ? OS measured by HR. ? The comparison will include all randomised participants, regardless of whether the participant withdraws from therapy or receives another anticancer therapy. NAME OF THE RESULT: To demonst | — |
Countries
Australia, Brazil, Canada, China, Colombia, France, Germany, Italy, Japan, Korea South, Peru, Poland, Portugal, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kindgdom, United States, Vietnam
Contacts
Public ContactDIANA ELIZABETH REVILLA
ASTRAZENECA PERU S.A.
Outcome results
None listed