What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) involving immune checkpoint inhibitors such as Durvalumab, Oleclumab, and Monalizumab often lead to side effects including fatigue, rash, diarrhea, and immune-related adverse events like pneumonitis, hepatitis, and colitis. When combined with chemotherapy, additional side effects may include neutropenia, febrile neutropenia, and hypertension. Severe adverse events can occur, and treatment-related deaths have been reported in some cases.

What prior FDA approvals exist?

Several immune checkpoint inhibitors have received FDA approval for the treatment of Non-Small Cell Lung Cancer (NSCLC). Pembrolizumab (Keytruda) is approved for use in combination with chemotherapy for first-line treatment of metastatic NSCLC and as monotherapy for tumors expressing PD-L1. Nivolumab (Opdivo) is approved for previously treated advanced NSCLC. Atezolizumab (Tecentriq) is approved for use with chemotherapy in both squamous and non-squamous NSCLC. These treatments target the PD-1/PD-L1 pathway, similar to the investigational combinations of Durvalumab with Oleclumab or Monalizumab being studied.

What other types of research exist?

Promising alternatives to Durvalumab with Oleclumab or Monalizumab for NSCLC patients include: 1) Pembrolizumab plus chemotherapy, which has shown improved OS and PFS in both squamous and nonsquamous NSCLC. 2) Atezolizumab plus chemotherapy, which is investigational for squamous NSCLC but has shown efficacy in nonsquamous NSCLC. 3) Nivolumab plus ipilimumab, which is being explored in combination with chemotherapy for advanced NSCLC.

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Checkpoint Inhibitor

Durvalumab + Oleclumab/Monalizumab for Lung Cancer (PACIFIC-9 Trial)

Phase 3

Recruiting

Led By Fabrice Barlesi, MD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Provision of a tumour tissue sample obtained prior to CRT

Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease

Must not have

Mixed small cell and non-small cell lung cancer histology

Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of randomization until 3 months after last dose of ip

Awards & highlights

Pivotal Trial

Summary

This trial is testing two drug combinations to help the immune system fight advanced lung cancer that can't be surgically removed. The patients have already had previous treatment without their disease getting worse. The drugs aim to boost the immune response to better identify and kill cancer cells.

Who is the study for?

Adults over 18 with Stage III unresectable Non-Small Cell Lung Cancer (NSCLC) who haven't worsened after platinum-based chemoradiation. They must have normal organ function, no history of certain autoimmune diseases or other cancers within the last 5 years, and not be on immunosuppressants.

What is being tested?

The study is testing Durvalumab in combination with either Oleclumab or Monalizumab against a placebo to see if they improve outcomes for NSCLC patients post-chemoradiation. It's randomized and double-blind, meaning neither doctors nor patients know who gets which treatment.

What are the potential side effects?

Durvalumab can cause immune-related side effects like inflammation in various organs, skin reactions, hormone gland problems, and infusion-related symptoms. Oleclumab and Monalizumab may also trigger similar immune responses.

Eligibility Criteria

Inclusion Criteria

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

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I have provided a tumor tissue sample before starting CRT.

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My lung cancer was confirmed by lab tests and treated with combined chemo and radiation for stage III.

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I have completed at least 2 cycles of chemotherapy with platinum drugs and radiation.

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I am fully active or able to carry out light work.

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I received a specific dose of radiation as part of my treatment.

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My cancer does not have changes in the EGFR or ALK genes.

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My condition did not worsen after receiving specific chemotherapy and radiation together.

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I am 18 years old or older.

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 non-small cell types.

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My Stage III NSCLC has worsened despite platinum-based treatments.

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I don't have lasting side effects from previous cancer treatments, except for hair loss.

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

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I am getting chemoradiation for Stage III non-small cell lung cancer that can't be removed with surgery.

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I have had lung inflammation from previous cancer treatments.

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I have had lung issues like fibrosis or pneumonia in the past 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of randomization until 3 months after date of last ip dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of randomization until 3 months after date of last ip dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of randomization until 3 months after date of last ip dose 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 Surival (PFS)

Secondary study objectives

Anti-drug antibodies (ADAs)

Concentration of Durvalumab

Concentration of Monalizumab

+12 more

Side effects data

From 2022 Phase 2 trial • 80 Patients • NCT03015129

65%

Fatigue

63%

Abdominal pain

55%

Diarrhea

43%

Pain

40%

Weight loss

35%

Hypertension

30%

Anorexia

30%

Constipation

28%

Nausea

28%

Pruritus

25%

Vomiting

20%

Dyspnea

20%

Urinary tract infection

18%

Rash maculo-papular

15%

Cough

15%

Abdominal Pain

15%

Back pain

15%

Increased Urinary Frequency

15%

Weight gain

13%

Arthralgia

10%

Dizziness

10%

Anxiety

10%

Bladder infection

10%

Nasal congestion

10%

Vaginal discharge

Colitis

Dry mouth

Dry skin

Fever

Anal pain

Edema limbs

Flatulence

Headache

Hot flashes

Myalgia

Small intestinal obstruction

Thromboembolic event

Urinary frequency

Urinary tract pain

Confusion

Renal and urinary disorders - Other, specify

Adrenal insufficiency

Anemia

Ascites

Gastroesophageal reflux disease

Hypomagnesemia

Lymphedema

Memory impairment

Mucositis oral

Pneumonitis

Rash acneiform

Sinus bradycardia

Upper respiratory infection

Urinary urgency

Vaginal hemorrhage

Alanine aminotransferase increased

Aspartate aminotransferase increased

Alkaline phosphatase increased

Colonic perforation

Dysarthria

Blood bilirubin increased

CPK increased

Creatinine increased

Myositis

Rectal hemorrhage

Hypothyroidism

Left ventricular systolic dysfunction

Lethargy

Muscle weakness left-sided

Myocarditis

Rectal pain

Weight Loss

Fall

Generalized muscle weakness

Hyperglycemia

Hyperkalemia

Pain in extremity

Peripheral sensory neuropathy

Pleural effusion

Skin infection

100%

80%

60%

40%

20%

Study treatment Arm

Durvalubmab

Durvalubmab + Tremelimumab

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm B: Durvalumab and MonalizumabExperimental Treatment3 Interventions

Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only

Group II: Arm A: Durvalumab and OleclumabExperimental Treatment2 Interventions

Durvalumab on Day 1 of each 28-day cycle + Oleclumab 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

Group III: Arm C: Durvalumab and PlaceboActive Control2 Interventions

Durvalumab on Day 1 of each 28-day cycle + Placebo 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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Monalizumab

2019

Completed Phase 2

~260

Oleclumab

2015

Completed Phase 2

~880

Durvalumab

2017

Completed Phase 2

~3750

0 / 15Eligibility 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

Immune checkpoint inhibitors, such as Durvalumab, Oleclumab, and Monalizumab, work by targeting specific proteins that regulate the immune system's ability to recognize and attack cancer cells. Durvalumab blocks the PD-L1 protein, preventing it from binding to the PD-1 receptor on T-cells, thereby enhancing the immune response against cancer cells. Oleclumab targets CD73, an enzyme involved in the production of adenosine, which suppresses immune activity; inhibiting CD73 can reduce this suppression and boost immune activity. Monalizumab targets the NKG2A receptor on natural killer (NK) cells and some T-cells, preventing it from inhibiting these cells' activity. By blocking these checkpoints, these treatments help the immune system to better identify and destroy cancer cells, which is crucial for NSCLC patients as it can lead to improved outcomes and potentially longer survival.

CCTG BR34: A Randomized Phase 2 Trial of Durvalumab and Tremelimumab With or Without Platinum-Based Chemotherapy in Patients With Metastatic NSCLC.