A Study to Determine Safety of Durvalumab After Sequential Chemo Radiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer

NCT03693300 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: D4194C000062018-002220-16
• Study Type: interventional
• Target: 117
• Locations: 6 countries
• Sites: 28

Brief Summary

This is a Phase II, open-label, multi-centre study to determine the safety of a fixed dose of Durvalumab (MEDI4736) (1500 mg) every 4 weeks \[q4w\] in participants with unresectable Stage III Non-Small Cell Lung Cancer (NSCLC), who have not progressed following platinum-based sequential chemoradiation therapy (sCRT). This study will be conducted in Europe and North America.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Keywords

Stage III Non-Small Cell Lung Cancer; Durvalumab; IV infusion immunoglobulin G (IgG); Antibody-dependent cellular cytotoxicity; Complement-dependent cytotoxicity; Monotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Grade 3 and Grade 4 Treatment-related Adverse Events (TRAEs)

  Safety and tolerability of Durvalumab as defined by Grade 3 and Grade 4 TRAEs following IV infusion administration was assessed.

  Up to 6 months

Secondary Outcomes (8)

• Progression-free Survival (PFS)

  From the first date of treatment until the date of objective disease progression or death (approximately upto 48 months)

• Percentage of Patients Progression-free at 12 Months

  From the first date of treatment until the date of objective disease progression or death (upto 12 months)

• Overall Survival (OS)

  From the first date of treatment until death due to any cause (approximately upto 48 months)

• Percentage of Patients Alive

  From the first date of treatment until the date of objective disease progression or death (12 months, 24 months, and 36 months)

• Objective Response Rate (ORR)

  From 8 weeks ±1 week after investigational product (IP) treatment initiation and continue every 8 weeks (q8w) ±1 week through 52 weeks and every 12 weeks (q12w) ±1 week until disease progression (approximately upto 48 months)

Study Arms (2)

WHO/ECOG PS 0 to 1 Cohort

EXPERIMENTAL

100-120 participants will receive 1500 mg Durvalumab (MEDI4736) monotherapy via IV infusion q4w for up to a maximum of 24 months (up to 26 doses/cycles) with the last administration at Week 104. The study drug should be discontinued prior to 24 months if there is clinical progression or confirmed radiological progression or if there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Drug: Durvalumab

WHO/ECOG PS 2 Cohort

EXPERIMENTAL

up to 30 participants will receive 1500 mg Durvalumab (MEDI4736) monotherapy via IV infusion q4w for up to a maximum of 24 months (up to 26 doses/cycles) with the last administration at Week 104. The study drug should be discontinued prior to 24 months if there is clinical progression or confirmed radiological progression or if there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Drug: Durvalumab

Interventions

Durvalumab DRUG

Participants will receive 1500 mg Durvalumab monotherapy via IV infusion q4w for up to a maximum of 24 months with the last administration at Week 104.

Also known as: MEDI4736

WHO/ECOG PS 0 to 1 Cohort; WHO/ECOG PS 2 Cohort

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• Provision of signed and dated written genetic informed consent prior to collection of sample for genetic analysis (optional).
• years or older at the time of signing the ICF.
• Histologically- or cytologically-documented NSCLC with locally-advanced, unresectable Stage III disease (according to the IASLC Staging Manual Version 8 \[IASLC 2016\]). Positron emission tomography (PET)/CT, MRI of the brain, and endobronchial ultrasound with biopsy are highly encouraged at diagnosis.
• Receipt of sCRT which must have been completed within 42 days prior to first IP dose administration in the study.
• The platinum-based chemotherapy regimen must contain cisplatin or carboplatin and 1 of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel or docetaxel), or pemetrexed, according to the local standard of care (SoC) regimens. Platinum-based chemotherapy containing cisplatin or carboplatin and gemcitabine is permitted under certain conditions - refer to bullet point 6(b).
• Patients must have received at least 2 cycles of platinum-based chemotherapy before radiation therapy. The interval between administration of the last dose of chemotherapy regimen and start of radiation therapy must be no more than 6 weeks. Consolidation chemotherapy after radiation is not permitted.
• (i) If the patient's platinum-based chemotherapy contained gemcitabine, no overlap between chemotherapy and radiation therapy is permitted.
• (ii) If the patient's platinum-based chemotherapy contained any of the agents listed in (a) other than gemcitabine, an overlap of 1 cycle of chemotherapy and radiation therapy is acceptable.
• (c) Patients must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy). Sites are encouraged to adhere to mean organ radiation dosing as follows: (i) Mean lung dose \<20 Gy and/or V20 \<35%; (ii) Mean oesophagus \<34 Gy; (iii) Heart V45 \<35% or V30 \<30%. Note: Sites should be aware of the recent RTOG 0617 Study data demonstrating that doses higher than 60 Gy may be associated with greater toxicity and worse efficacy.
• (d) Patients with WHO/ECOG PS 2 or chronic lung disease (pulmonary emphysema or chronic obstructive pulmonary disease) must have received a V20 \<25%.
• Patients must not have progressed following platinum-based sCRT, as per Investigator assessed RECIST 1.1 criteria. . In order to assess disease progression, the baseline imaging (CT/MRI) used for Screening purposes should be compared against the most recently performed scan that allows physician assessment as per RECIST 1.1 criteria. If an intermediate scan taken between chemotherapy and radiotherapy is available and that scan is suitable for physician assessment as per RECIST 1.1 criteria, then this scan should be used.
• Patients with measurable disease and/or non-measurable and/or no evidence of disease (NED) assessed at baseline by CT/MRI will be entered in this study.
• Prior irradiated lesions may be considered measurable and selected as TLs provided they fulfil the other criteria for measurability.

You may not qualify if:

• Patients with locally-advanced NSCLC whose disease has progressed following platinum based sCRT.
• Patients who have disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumours.
• Mixed small-cell lung cancer and NSCLC histology.
• History of allogeneic organ transplantation.
• 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 syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 5 years at enrolment may be included but only after consultation with the Study Physician.
• Patients with celiac disease controlled by diet alone.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, ILD, serious chronic GI conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (28)

Research Site

Gainesville, Georgia, 30501, United States

Location

Research Site

Knoxville, Tennessee, 37920, United States

Location

Research Site

Créteil, 94010, France

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Research Site

Paris, 75248, France

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Research Site

Saint-Priest-en-Jarez, 42270, France

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Research Site

Toulouse, 31400, France

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Research Site

Gauting, 82131, Germany

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Research Site

Großhansdorf, 22927, Germany

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Research Site

Hamm, 59063, Germany

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Research Site

Hanover, 30459, Germany

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Research Site

Heidelberg, 69126, Germany

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Research Site

Avellino, 83100, Italy

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Research Site

Meldola, 47014, Italy

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Research Site

Milan, 20133, Italy

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Research Site

Monza, 20900, Italy

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Research Site

Parma, 43126, Italy

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Research Site

Roma, 00152, Italy

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Research Site

Barcelona, 08907, Spain

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Research Site

Guadalajara, 19002, Spain

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Madrid, 28041, Spain

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Research Site

Seville, 41013, Spain

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Valencia, 46015, Spain

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Research Site

Leeds, LS9 7TF, United Kingdom

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Research Site

Manchester, M20 4BX, United Kingdom

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Research Site

Middlesbrough, TS4 3BW, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Sheffield, S10 2SJ, United Kingdom

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Research Site

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Related Publications (1)

• Garassino MC, Mazieres J, Reck M, Chouaid C, Bischoff H, Reinmuth N, Cove-Smith L, Mansy T, Cortinovis D, Migliorino MR, Delmonte A, Sanchez JG, Chara Velarde LE, Bernabe R, Paz-Ares L, Perez ID, Trunova N, Foroutanpour K, Faivre-Finn C. Durvalumab After Sequential Chemoradiotherapy in Stage III, Unresectable NSCLC: The Phase 2 PACIFIC-6 Trial. J Thorac Oncol. 2022 Dec;17(12):1415-1427. doi: 10.1016/j.jtho.2022.07.1148. Epub 2022 Aug 9.

  PMID: 35961520 DERIVED

Related Links

• CSP Redacted
• SAP Redacted
• CSR Synopsis Redacted

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: October 2, 2018
• Study Start: April 16, 2019
• Primary Completion: December 13, 2022
• Study Completion: April 21, 2023
• Last Updated: June 18, 2024
• Results First Posted: October 7, 2022

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

ES (5); US (2); GB (6); FR (4); DE (5); IT (6)