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NKG2A inhibition

CompoundMonalizumab

Area under investigation

NSCLC

Scientific PillarImmuno-Oncology

 

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PACIFIC-9 trial overview

Tumor

Unresectable stage III NSCLC not progressed following definitive platinum-based cCRT

Trial Identifier

NCT05221840

Phase

III

Stage

Unresectable Stage III

Regimen

Durvalumab + oleclumab; durvalumab + monalizumab; durvalumab + placebo

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Study Design

Inclusion criteria

The key inclusion criteria are –

  • Age ≥18 years
  • Histologically or cytologically documented NSCLC and have been treated with cCRT for locally advanced, unresectable stage III disease
  • Provision of a tumor tissue sample obtained prior to CRT
  • Documented tumor PD-L1 status by central lab
  • Documented EGFR and ALK wild-type status (local or central)
  • At least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy with no disease progression
  • Adequate organ and bone marrow function
  • WHO PS 0-1
  • Total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy prior to randomizationa

 

aRadiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.

 

Reference:

Study NCT05221840. ClinicalTrials.gov website.

Exclusion criteria

The key exclusion criteria are –

  • Mixed small cell and non-small cell lung cancer histology
  • Sequential (not inclusive of induction) chemoradiation therapy for locally advanced stage III unresectable NSCLC
  • Progression during platinum-based cCRT
  • Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia)
  • Grade ≥2 pneumonitis from prior chemoradiation therapy
  • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis – regardless of time of onset prior to randomization. Evidence of active non-CRT-induced pneumonitis (grade ≥2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis – diagnosed in the past 6 months prior to randomization
  • Active or prior documented autoimmune or inflammatory disorders (with exceptions)
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
  • 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, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumors without evidence of disease
  • Patients with a history of myocardial infarction, transient ischemic attack, stroke, or pulmonary embolism diagnosed in the past 6 months or venous thrombosis diagnosed in the past 3 months prior to the scheduled first dose of study treatment

Study Locator

Explore further trial details, understand eligibility criteria and speak to clinical trial navigators for the PACIFIC-9 trial via the Lung Cancer Study Locator website.

Visit Study Locator

PACIFIC-9 Overview Modal

PACIFIC-9 trial overview

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PACIFIC-9 trial overview

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Target Overview

NKG2A is an immune checkpoint inhibitor receptor that is expressed on NK cells, as well as tumor-infiltrating CD8+ T cells.1,2 Its natural ligand, HLA-E, is highly expressed on many solid and hematologic tumors.3,4 Binding of tumor-associated HLA-E to NKG2A inhibits NK cell and CD8+ T-cell activation and ablates NK cell and CD8+ T-cell–mediated antitumor killing.5,6

Compound Overview

Monalizumaba is an investigational anti-NKG2A antibody that binds to NKG2A on NK cells and intratumoral CD8+ T cells and helps block the inhibitory interactions between tumor-associated HLA-E and the NKG2A receptor. This, in turn, may enhance innate immune antitumor responses. 

aAstraZeneca has a co-development agreement with Innate Pharma to develop monalizumab in oncology.

Mechanism of Action

  • Mechanism of Action

Reference: Martinez-Marti et al. ESMO 2021 oral presentation (LBA42).

References

1. Platonova S, Cherfils-Vicini J, Damotte D, et al. Cancer Res. 2011;71(16):5412-5422. 2. Sheu B-C, Chiou S-H, Lin H-H, et al. Cancer Res. 2005;65(7):2921-2929. 3. Braud VM, Allan DS, O’Callaghan CA, et al. Nature. 1998;391(6669):795-799. 4. Talebian Yazdi M, van Riet S, van Schadewijk A, et al. Oncotarget. 2016;7(3):3477-3488. 5. Pace E, Di Sano C, Ferraro M, et al. Eur J Cancer. 2011;47(2):296-304. 6. Speiser DE, Pittet MJ, Valmori D, et al. J Exp Med. 1999;190(6):775-782.

 

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PACIFIC-9 trial overview

Tumor

Unresectable stage III NSCLC not progressed following definitive platinum-based cCRT

Trial Identifier

NCT05221840

Phase

III

Stage

Unresectable Stage III

Regimen

Durvalumab + oleclumab; durvalumab + monalizumab; durvalumab + placebo

Visit ct.gov

Study Design

Inclusion criteria

The key inclusion criteria are –

  • Age ≥18 years
  • Histologically or cytologically documented NSCLC and have been treated with cCRT for locally advanced, unresectable stage III disease
  • Provision of a tumor tissue sample obtained prior to CRT
  • Documented tumor PD-L1 status by central lab
  • Documented EGFR and ALK wild-type status (local or central)
  • At least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy with no disease progression
  • Adequate organ and bone marrow function
  • WHO PS 0-1
  • Total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy prior to randomizationa

 

aRadiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.

 

Reference:

Study NCT05221840. ClinicalTrials.gov website.

Exclusion criteria

The key exclusion criteria are –

  • Mixed small cell and non-small cell lung cancer histology
  • Sequential (not inclusive of induction) chemoradiation therapy for locally advanced stage III unresectable NSCLC
  • Progression during platinum-based cCRT
  • Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia)
  • Grade ≥2 pneumonitis from prior chemoradiation therapy
  • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis – regardless of time of onset prior to randomization. Evidence of active non-CRT-induced pneumonitis (grade ≥2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis – diagnosed in the past 6 months prior to randomization
  • Active or prior documented autoimmune or inflammatory disorders (with exceptions)
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
  • 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, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumors without evidence of disease
  • Patients with a history of myocardial infarction, transient ischemic attack, stroke, or pulmonary embolism diagnosed in the past 6 months or venous thrombosis diagnosed in the past 3 months prior to the scheduled first dose of study treatment

Study Locator

Explore further trial details, understand eligibility criteria and speak to clinical trial navigators for the PACIFIC-9 trial via the Lung Cancer Study Locator website.

Visit Study Locator

PACIFIC-9 Overview Modal

PACIFIC-9 trial overview

Take me to ClinicalTrials.Gov

You are now leaving the AstraZeneca Oncology Portfolio.
You have selected a link that will take you to a site maintained by a third party.

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PACIFIC-9 Study Modal

PACIFIC-9 trial overview

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Abbreviations

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  • ADCC

    antibody-dependent cellular cytotoxicity

  • ALK

    anaplastic lymphoma kinase

  • BICR

    blinded independent central review

  • cCRT

    concurrent chemoradiation therapy

  • DoR

    duration of response

  • EGFR

    epidermal growth factor receptor

  • HLA-E

    HLA class I histocompatibility antigen E

  • HNSCC

    head and neck squamous cell carcinoma

  • IV

    intravenous

  • NK

    natural killer

  • NKG2A

    natural killer cell lectin-like receptor

  • NSCLC

    non-small cell lung cancer

  • ORR

    overall or objective response rate

  • OS

    overall survival

  • PD-1

    programmed cell death-1

  • PD-L1

    programmed cell death ligand-1

  • PDC

    platinum doublet chemotherapy

  • PFS

    progression-free survival

  • PFS2

    time to second progression or death

  • Q*W

    every * weeks

  • Q4W

    every 4 weeks

  • R

    randomization

  • RECIST

    Response Evaluation Criteria in Solid Tumors

  • TFST

    time to first subsequent therapy

  • TTDM

    time to death or distant metastases

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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