Clinical trial NCT03775486: Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION)
Official title: A Phase II Randomized, Multi-Center, Double-Blind, Global Study to Determine the Efficacy and Safety of Durvalumab Plus Olaparib Combination Therapy Compared With Durvalumab Monotherapy as Maintenance Therapy in Patients Whose Disease Has Not Progressed Following Standard of Care Platinum-Based Chemotherapy With Durvalumab in First Line Stage IV Non Small Cell Lung Cancer (ORION)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer NSCLC
Keywords: NSCLC
Durvalumab
Olaparib
Maintenance
Homologous Recombination Repair (HRR)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-12-14
Enrollment: 401
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, multi-center, global Phase II study to determine the efficacy and safety of Durvalumab plus Olaparib combination therapy compared with Durvalumab monotherapy as maintenance therapy in patients whose disease has not progressed following Standard of Care (SoC) platinum-based chemotherapy with Durvalumab as first-line treatment in patients with Stage IV non small-cell lung cancer (NSCLC) with tumors that lack activating epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions.

Detailed description: Adult patients with a histologically or cytologically documented advanced NSCLC not amenable to curative surgery or radiation with tumors that lack activation EGFR mutations and ALK fusions are eligible for enrollment. During the initial therapy phase, patients will receive treatment with Durvalumab along with the Investigator's choice of platinum-based doublet therapy for squamous NSCLC (nab-paclitaxel plus carboplatin or gemcitabine plus carboplatin/cisplatin) and non-squamous NSCLC (nab-paclitaxel plus carboplatin or pemetrexed plus carboplatin/cisplatin) for 4 cycles. Patients who have completed 4 cycles and not progressed throughout the initial therapy phase will be randomized in a 1:1 ratio into the maintenance phase of the study to receive either Durvalumab plus placebo or Durvalumab plus Olaparib maintenance therapy. Patients will receive maintenance treatment until specific discontinuation criteria are met, including clinical disease progression (as assessed by the Investigator) or RECIST 1.1-defined radiological Progressive Disease (PD), unacceptable toxicity, and withdrawal of consent. Tumor evaluation scans will be performed until objective disease progression as efficacy assessments. All patients will be followed for survival until the end of the study.

Eligibility criteria: Inclusion Criteria:

- Histologically or cytologically documented Stage IV NSCLC not amenable to curative surgery or radiation.

Patients must have tumors that lack activating EGFR mutations and ALK fusions.

* (WHO)/(ECOG) performance status of 0 or 1
* No prior chemotherapy or any other systemic therapy for Stage IV NSCLC
* Adequate organ and marrow function without blood transfusions in the past 28 days,
* At least 1 tumor lesion, not previously irradiated, that can be accurately measured as per RECIST 1.1.

Key Inclusion criteria for randomization to maintenance treatment:

* Documented radiographic evidence of CR, PR, or Stable Disease (SD) as per Investigator-assessed RECIST 1.1 following 4 cycles of platinum-based chemotherapy.
* Creatinine Clearance (CrCl) ≥51 mL/min calculated by the investigator or designee using the Cockcroft-Gault equation or measured by 24-hour urine collection.
* Ability to swallow whole oral medications.
* All patients must provide a formalin-fixed, paraffin embedded tumor sample for tissue-based immunohistochemistry staining and DNA sequencing to determine PD-L1 expression, HRRm status, and other correlatives: either newly acquired or archival tumor samples (\<3 years old) are acceptable. If available, a newly acquired tumor biopsy, collected as part of routine clinical practice, is preferred. If not available, an archival sample taken \<3 years prior to screening is acceptable. If both an archival sample and a fresh tumor biopsy sample are available, both samples should be submitted for analysis and must be submitted as different samples using different accession numbers. Slides from different blocks cannot be mixed and submitted with the same kit.

Exclusion criteria

* Mixed small-cell lung cancer and sarcomatoid variant NSCLC histology.
* Prior exposure to any chemotherapy agents (except chemotherapy or chemoradiation for non-metastatic disease), polyadenosine 5'diphosphoribose \[poly (ADP ribose)\] polymerase (PARP) therapy, or immunomediated therapy
* Active or prior documented autoimmune or inflammatory disorders.
* Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of Investigational Product (IP)
* untreated (CNS) metastases and/or carcinomatous meningitis
* Active infection.

Exclusion criteria to be randomized to maintenance treatment:

• Inability to complete 4 cycles of platinum-based chemotherapy for any reason or discontinuation of Durvalumab during initial therapy.

Primary outcomes:
measure: Progression-free Survival
timeFrame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization until the date of death due to any cause, up to 18 months.
measure: Objective Response Rate
timeFrame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
measure: Duration of Response
timeFrame: From date of first documented response until objective radiological disease progression or death, up to 18 months.
measure: Progression-free Survival in Homologous Recombination Repair Related Gene Mutation (HRRm) Population
timeFrame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
measure: Concentration of Durvalumab
timeFrame: Assessed from start of initial therapy up to 2 years.
measure: Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13
timeFrame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
measure: Time to Deterioration in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13
timeFrame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
measure: Change From Baseline in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30
timeFrame: Includes all assessments occurring within the first 12 months of randomization or until disease progression, up to 18 months.
measure: Time to Deterioration in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30
timeFrame: From randomization until date of first symptom deterioration that is confirmed, up to 18 months.
measure: Presence of Anti-drug Antibodies (ADAs) for Durvalumab
timeFrame: Assessed from start of initial therapy up to 2 years.
measure: Number of Participants With Treatment-Related Adverse Events
timeFrame: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months
Other outcomes:
Locations:
city: Bonita Springs
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Tallahassee
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Bethlehem
country: United States
facility: Research Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Aalst
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Roeselare
country: Belgium
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Deszk
country: Hungary
facility: Research Site
city: Farkasgyepü
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Jamnagar
country: India
facility: Research Site
city: Kochi
country: India
facility: Research Site
city: Mysuru
country: India
facility: Research Site
city: Nashik
country: India
facility: Research Site
city: Nashik
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Thiruvananthapuram
country: India
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kanazawa-shi
country: Japan
facility: Research Site
city: Kurume-shi,
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Ube-shi
country: Japan
facility: Research Site
city: Dongjakgu
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Seodaemun-gu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suweonsi Paldalgu
country: Korea, Republic of
facility: Research Site
city: Chihuahua
country: Mexico
facility: Research Site
city: Culiacan
country: Mexico
facility: Research Site
city: San Luis Potosí
country: Mexico
facility: Research Site
city: Blaricum
country: Netherlands
facility: Research Site
city: Harderwijk
country: Netherlands
facility: Research Site
city: Tilburg
country: Netherlands
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Prabuty
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Kursk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nal'chik
country: Russian Federation
facility: Research Site
city: P. Herzen Moscow Oncology Rese
country: Russian Federation
facility: Research Site
city: Sochi
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Kharkiv Region
country: Ukraine
facility: Research Site
city: Kirovohrad
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Uzhhorod
country: Ukraine
facility: Research Site
city: Zaporizhzhia
country: Ukraine
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: Hull
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Sungkyunkwan University School of Medicine, 135-710, Seoul, Korea
name: Myung-Ju Ahn, MD
role: PRINCIPAL_INVESTIGATOR
References: