What side effects are associated with this type of intervention?

Common treatments for NSCLC, particularly those involving PD-L1 inhibitors like Durvalumab and PARP inhibitors like Olaparib, are associated with a range of side effects. PD-L1 inhibitors can cause immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Severe (grade 3 or higher) adverse events are also common, including fatigue, nausea, and increased liver function tests. PARP inhibitors like Olaparib may lead to side effects such as anemia, nausea, fatigue, and potential myelodysplastic syndrome or acute myeloid leukemia. Combination therapies, such as Durvalumab with chemotherapy, often result in higher rates of severe adverse events, including neutropenia, febrile neutropenia, and hypertension.

What prior FDA approvals exist?

For the treatment of Non-Small Cell Lung Cancer (NSCLC), the FDA has approved several PD-L1 inhibitors, including Durvalumab, Pembrolizumab, and Atezolizumab. These drugs have shown efficacy in improving overall survival and progression-free survival in various clinical trials, often in combination with chemotherapy. Pembrolizumab, for instance, is approved for use in combination with chemotherapy for patients with advanced NSCLC and as monotherapy for tumors with high PD-L1 expression. Atezolizumab is approved for use in combination with bevacizumab and chemotherapy for non-squamous NSCLC. While PARP inhibitors like Olaparib are primarily approved for ovarian and breast cancers, their combination with PD-L1 inhibitors in NSCLC is currently under investigation in clinical trials.

What other types of research exist?

Promising alternatives to Durvalumab plus Olaparib for NSCLC patients include: 1) Sintilimab plus pemetrexed and platinum, which has shown promising efficacy in a phase 3 study for nonsquamous NSCLC. 2) Pembrolizumab plus chemotherapy, which has demonstrated improved OS and PFS in both squamous and nonsquamous NSCLC in the KEYNOTE-407 and KEYNOTE-189 trials. 3) Atezolizumab plus chemotherapy, which has shown benefits in specific subgroups of NSCLC patients, particularly those with high PD-L1 expression.

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Durvalumab + Olaparib for Non-Small Cell Lung Cancer (ORION Trial)

Phase 2

Waitlist Available

Led By Myung-Ju Ahn, MD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

No prior chemotherapy or any other systemic therapy for Stage IV NSCLC

Ability to swallow whole oral medications

Must not have

Mixed small-cell lung cancer and sarcomatoid variant NSCLC histology

Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up assessed from start of initial therapy up to 2 years.

Summary

This trial is testing a combination of two drugs, Durvalumab and Olaparib, against using just Durvalumab alone. It targets adults with advanced lung cancer that cannot be treated with surgery or radiation and lacks certain genetic mutations. Durvalumab helps the immune system attack cancer, while Olaparib prevents cancer cells from repairing themselves. Durvalumab is a standard drug used after initial treatment in patients with advanced non-small cell lung cancer.

Who is the study for?

This trial is for Stage IV non-small cell lung cancer patients without certain genetic mutations, who've had no prior systemic therapy and responded to initial chemo with Durvalumab. They must be able to perform daily activities with little or no assistance, swallow pills, and have proper kidney function and organ health.

What is being tested?

The ORION study tests if adding Olaparib to Durvalumab maintenance therapy is more effective than Durvalumab alone after initial chemo in advanced lung cancer patients. It's a global Phase II trial where participants are randomly assigned treatment options in a blinded manner.

What are the potential side effects?

Durvalumab may cause immune-related issues like inflammation of organs, while Olaparib can lead to blood cell count changes, nausea, fatigue, respiratory infections and potential allergic reactions. Side effects vary among individuals.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have not received any treatment for stage IV non-small cell lung cancer.

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I can swallow pills whole.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have at least one tumor that can be measured and has not been treated with radiation.

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My cancer does not have EGFR mutations or ALK fusions.

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My kidney function, measured by creatinine clearance, is good.

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My lung cancer is at stage IV and cannot be cured with surgery or radiation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My lung cancer is a mix of small-cell and sarcomatoid types.

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I am not currently on any cancer treatments like chemotherapy or hormone therapy.

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I haven't taken immunosuppressive drugs in the last 14 days.

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I have brain metastases or carcinomatous meningitis that hasn't been treated.

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I currently have an infection.

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I have or had an autoimmune or inflammatory disorder.

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I couldn't complete 4 cycles of platinum-based chemotherapy or stopped taking Durvalumab during the first treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ assessed from start of initial therapy up to 2 years.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~assessed from start of initial therapy up to 2 years.

This trial's timeline: 3 weeks for screening, Varies for treatment, and assessed from start of initial therapy up to 2 years. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free Survival

Secondary study objectives

Change From Baseline in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30

Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13

Concentration of Durvalumab

+8 more

Side effects data

From 2023 Phase 3 trial • 154 Patients • NCT02184195

49%

Nausea

47%

Fatigue

38%

Diarrhoea

29%

Abdominal pain

29%

Anaemia

28%

Constipation

27%

Decreased appetite

27%

Back pain

26%

Vomiting

21%

Arthralgia

19%

Pyrexia

18%

Asthenia

13%

Rash

13%

Nasopharyngitis

11%

Alanine aminotransferase increased

11%

Dyspnoea

10%

Neuropathy peripheral

10%

Cough

10%

Abdominal pain upper

10%

Dyspepsia

10%

Anxiety

10%

Pruritus

Dizziness

Hyperglycaemia

Aspartate aminotransferase increased

Thrombocytopenia

Oedema peripheral

Pain in extremity

Insomnia

Stomatitis

Dry mouth

Headache

Neutropenia

Blood creatinine increased

Weight decreased

Dysgeusia

Blood alkaline phosphatase increased

Neutrophil count decreased

Muscle spasms

Influenza

Influenza like illness

Myalgia

Peripheral sensory neuropathy

Gamma-glutamyltransferase increased

Hypertension

Platelet count decreased

Depression

Lymphopenia

Gastrooesophageal reflux disease

Abdominal distension

Musculoskeletal pain

Flank pain

Cholangitis

Flatulence

Paraesthesia

General physical health deterioration

Bladder papilloma

Pneumonia pneumococcal

Abdominal infection

Bartholinitis

Pneumonia

Cerebrovascular accident

Pneumothorax

Gastric varices haemorrhage

Large intestinal obstruction

Cholecystitis

Anastomotic haemorrhage

Device occlusion

Stent malfunction

Bronchiolitis

Empyema

Syncope

Incisional hernia

Device dislocation

Obstruction gastric

Cardiac failure

Vascular stenosis

Pleural effusion

Incarcerated inguinal hernia

Urinary tract infection

Hypothyroidism

Transient ischaemic attack

Infusion related reaction

Duodenal perforation

Melaena

Bile duct obstruction

Pancreatitis

100%

80%

60%

40%

20%

Study treatment Arm

Olaparib 300 mg Twice Daily (bd)

Placebo

Trial Design

2Treatment groups

Experimental Treatment

Group I: Durvalumab/Olaparib Combination TherapyExperimental Treatment7 Interventions

Durvalumab/Olaparib Combination Therapy: Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/Olaparib (maintenance phase)

Group II: Durvalumab MonotherapyExperimental Treatment7 Interventions

Durvalumab Monotherapy: Durvalumab/SoC chemotherapy (initial therapy phase) followed by Durvalumab/placebo (maintenance phase)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Durvalumab

2017

Completed Phase 2

~3750

Olaparib

2007

Completed Phase 4

~2190

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include immune checkpoint inhibitors and PARP inhibitors. Immune checkpoint inhibitors, such as Durvalumab, target the PD-L1 protein on cancer cells, preventing them from evading the immune system. This allows the body's immune cells to recognize and attack the cancer. PARP inhibitors, like Olaparib, block the PARP enzyme involved in DNA repair, leading to the accumulation of DNA damage in cancer cells, which ultimately causes cell death. These mechanisms are crucial for NSCLC patients as they offer targeted approaches to disrupt cancer cell survival and enhance the immune response, potentially improving treatment outcomes.

CCTG BR34: A Randomized Phase 2 Trial of Durvalumab and Tremelimumab With or Without Platinum-Based Chemotherapy in Patients With Metastatic NSCLC.Rationale and design of a phase II trial of durvalumab treatment in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy (SPIRAL-RT study).