Imaging Tumor-infiltrating T-cells in Non-small Cell Lung Cancer

NCT03853187 | Completed Phase 2

• 3 other identifiers: ESR-17-13332NL68987.091.192019-000670-37
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is an interventional study, to assess feasibility and safety of durvalumab (MEDI4736) in neo-adjuvant setting in patients with resectable NSCLC. Additional analyses of potential imaging biomarkers, e.g. Zr-89 labelled durvalumab (MEDI4736), ex vivo In-111-oxine labelled CD8+ T-cells and high-resolution immune cell imaging, in relation to immunotherapy induced immune responses on quantitative immune histochemical analysis of the resected tumor specimen, will be performed.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Safety of neo-adjuvant durvalumab: number of NCI CTCAE v 5.0 grade ≥3

  Demonstrate safety of two courses durvalumab (MEDI4736) 750 mg at two weeks interval in neo-adjuvant setting. Safety is defined as the number of NCI CTCAE v 5.0 grade ≥3 toxicity related to neo-adjuvant durvalumab (MEDI4736).

  14 days

• Feasibility of neo-adjuvant durvalumab: successful completion of curative surgery

  Demonstrate feasibility of two courses durvalumab (MEDI4736) 750 mg at two weeks interval in neo-adjuvant setting. Feasibility is defined as successful completion of curative surgery within 42 days after start of neo-adjuvant treatment with durvalumab (MEDI4736) (= day 1).

  42 days

Secondary Outcomes (13)

• Imaging related_response on CE-CT

  42 days

• Imaging related_pathological response

  42 days

• Imaging related_correlation with Zr89-labelled durvalumab

  42 days

• Imaging related_correlation with perfusion-CT

  42 days

• Biomarker related_future correlation with other biomarkers

  42 days

Study Arms (1)

Durvalumab (MEDI4736) neo-adjuvant

EXPERIMENTAL

Patients will receive two courses of durvalumab (MEDI4736)at a fixed dose of 750mg Q2W intravenously, prior to scheduled resection of NSCLC. Patients are amendable to adjuvant chemo and/or radiation treatment, per standard-of-care. Additionally, patients will undergo a Zr-89 labelled durvalumab (MEDI4736) PET/CT and dedicated perfusion-CT prior to treatment with durvalumab (MEDI4736) and ex vivo In-111-oxine or in vivo \[89Zr\]-Df-crefmirlimab labelled CD8+ T-cells after two courses of treatment, prior to surgery.

Radiation: Zr-89 labelled durvalumab PET/CT; Drug: Durvalumab (MEDI4736)

Interventions

Zr-89 labelled durvalumab PET/CT RADIATION

Patients will undergo a Zr-89 labelled durvalumab (MEDI4736) PET/CT and dedicated perfusion-CT prior to treatment with durvalumab (MEDI4736) and in- and ex-vivo In-111-oxine or in-vivo \[89zr\]-Df-crefmirlimab labelled CD8+ T-cells after two courses of treatment, prior to surgery.

Also known as: In-111-oxine labelled CD8+ T-cell scintigraphy OR [89Zr]-Df-crefmirlimab PET, Dedicated perfusion-CT

Durvalumab (MEDI4736) neo-adjuvant

Durvalumab (MEDI4736) DRUG

Patients will receive two courses of durvalumab (MEDI4736)at a fixed dose of 750mg Q2W intravenously, prior to scheduled resection of NSCLC.

Durvalumab (MEDI4736) neo-adjuvant

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged \>50 years at time of study entry
• Histopathological proven primary non-small cell lung cancer, with fully evaluable histological biopsies available
• ECOG performance status of 0 or 1
• AJCC stage I, II or IIIa as determined by contrast-enhanced CT chest-abdomen and F-18-FDG PET/CT: cT1cN0-1M0, cT2aN0-1M0 en cT3N0-1M0 (T3 separate nodule)
• Solid appearance of the tumor on contrast-enhanced CT
• Scheduled for resection with curative intent
• Patients should be medically operable defined by:
• Sufficient cardiopulmonary function
• Major contra-indications for surgery.
• No underlying immune disease (neutro- or lymphopenia, coagulation disorders) that could interfere with T-cell isolation
• Capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g, Health Insurance Portability and Accountability Act in the US, European Union Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Must have a life expectancy of at least 6 months
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL

You may not qualify if:

• Inability to lie supine for more than 30 minutes
• Documented previous severe allergic reaction to iodine-based contrast media, despite adequate pre-medication. In case of documented mild to moderate allergic reaction to iodine-based contrast media, patients will receive premedication according to the local protocol, consisting of 25mg prednisolone intravenously 30 minutes prior to iodine-based contrast media administration and 2mg clemastine intravenously just prior to administration.
• Indication for cervical mediastinoscopy according to the local multidisciplinary Thoracic-Oncology meeting
• Participation in another clinical study with an investigational product during the past 6 months
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) \<6 months prior to the first dose of study drug
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab (MEDI4736) may be included only after consultation with the Study Physician.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 6 months of the first dose of study drug
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], 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 (e.g., following Hashimoto syndrome) stable on hormone replacement

Sponsors & Collaborators

• Radboud University Medical Center: lead
• AstraZeneca: collaborator

Study Sites (1)

Radboud University Medical Center

Nijmegen, 6500 HB, Netherlands

Location

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

Study Officials

• Erik Aarntzen, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Michel van den Heuvel, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Jolanda de Vries, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 25, 2019
• Study Start: September 19, 2019
• Primary Completion: December 6, 2022
• Study Completion: December 6, 2022
• Last Updated: December 7, 2022

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)