Efficacy & Safety of rAd-IFN Administered With Celecoxib & Gemcitabine in Patients With Malignant Pleural Mesothelioma

NCT03710876 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: rAd-IFN-MM-3012017-003169-82
• Study Type: interventional
• Target: 53
• Locations: 9 countries
• Sites: 29

Brief Summary

This study will evaluate intrapleural administration of Adenovirus-Delivered Interferon Alpha-2b (rAd-IFN) in combination with Celecoxib and Gemcitabine in patients with histologically confirmed Malignant Pleural Mesothelioma (MPM) who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen. Eligible patients will be randomized 1:1 to either:

1. 1.Treatment group: rAd-IFN + Celecoxib followed by Gemcitabine
2. 2.Control group: Celecoxib followed by Gemcitabine

Conditions

Malignant Pleural Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Time to death (from any cause) from randomization

  4 years and 8 months

Secondary Outcomes (4)

• Progression Free Survival

  4 years and 8 months

• Best Response: Objective Response Rate (ORR)

  4 years and 8 months

• Best Response: Disease Control Rate (DCR)

  4 years and 8 months

• Best Response: Clinical Benefit Rate (CBR)

  4 years and 8 months

Other Outcomes (7)

• Survival Rate at 12 Months

  12 months

• Survival Rate at 18 Months

  18 months

• Survival Rate at 24 Months

  24 months

Study Arms (2)

Treatment Group

ACTIVE COMPARATOR

rAd-IFN (Study Day 1) + celecoxib (Study Days 1 to 14) + gemcitabine (Study Days 14 and 21 \[i.e., Days 1 and 8 of the first gemcitabine treatment cycle\], gemcitabine will be administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and repeated every 3 weeks until disease progression/early termination \[ET\]

Biological: rAd-IFN; Drug: Celecoxib Oral Product; Drug: Gemcitabine

Control Group

PLACEBO COMPARATOR

Celecoxib (Study Days 1 to 14) + gemcitabine (Study Days 14 and 21 \[i.e., Days 1 and 8 of the first gemcitabine treatment cycle\], gemcitabine will be administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and repeated every 3 weeks until disease progression/ET.

Drug: Celecoxib Oral Product; Drug: Gemcitabine

Interventions

rAd-IFN BIOLOGICAL

Adenovirus-Delivered Interferon Alpha-2b

Also known as: Nadofaragene firadenovec

Treatment Group

Celecoxib Oral Product DRUG

400 mg twice daily

Also known as: COX II Inhibitor

Control Group; Treatment Group

Gemcitabine DRUG

1250 mg/m2 administered intravenously on Days 1 and 8 of a 21-day cycle and continued every 3 weeks until disease progression/ early termination

Also known as: Chemotherapy

Control Group; Treatment Group

Eligibility Criteria

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

You may qualify if:

• Patients who meet all of the following criteria will be eligible to participate in the study:
• Aged 18 years or older at the time of consent;
• Able to give informed consent;
• Has a confirmed histological diagnosis of MPM with histological type epithelioid or biphasic (if biphasic, histology must be predominantly \[50%\] epithelioid). Histological diagnosis of MPM will be confirmed centrally using specimens or slides from tumor specimens obtained at the time of initial presentation or a subsequent procedure. Central confirmation of diagnosis with immunohistochemistry will be performed, and independent central confirmation will be required for study entry;
• Measurable disease, per modified Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 (see Section 7) for pleural mesothelioma;
• Has received a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, which may have been chemotherapeutic and/or immunotherapeutic treatment regimens for MPM which included at least 1 anti-folate and platinum combination regimen;
• Adjuvant or neoadjuvant therapy represent 1 line of therapy each;
• Treatment that is split between pre-surgical resection and post-surgical resection and is the same regimen will be counted as 1 regimen. Patients meeting this condition should be discussed with the Medical Monitor prior to including the patient in the study;
• Has a pleural space accessible for IPC or similar device insertion. Patients with a previously inserted IPC or similar device may be enrolled, and the pre-existing IPC or similar device can be used for vector administration as long as it is functional and has no evidence of local infection;
• Life expectancy 12 weeks in the judgement of the Investigator;
• Eastern Cooperative Oncology Group (ECOG) status of 1 or 0;
• Female and male patients:
• Female patients of childbearing potential must have a negative pregnancy test upon entry into this study and agree to use a highly effective method of contraception from Screening until 1 month after the last dose of gemcitabine;
• Highly effective methods of contraception that result in a low failure rate (i.e., \<1% per year) when used consistently and correctly include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence;
• True abstinence, when in line with the preferred and usual lifestyle of the patient, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of study participation and for 1 month after the last dose of gemcitabine. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, and post-ovulation method) and withdrawal are not acceptable methods of contraception; and

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from participation in the study:
• Is "treatment-naïve" (i.e., has not received at least 1 anti-folate and platinum combination regimen);
• Has previously received 3 or more lines of systemic chemotherapeutic or immunotherapeutic treatment. Treatment that is split between pre-surgical resection and post-surgical resection and is the same regimen will be counted as 1 regimen. Patients meeting this condition should be discussed with the Medical Monitor prior to including the patient in the study;
• Has previously received treatment with gemcitabine;
• Has stage IV extrathoracic metastatic disease;
• Inadequate pulmonary function of clinical significance as per Investigator review;
• Clinically significant pericardial effusion (i.e., as judged by the Investigator and/or requiring drainage) detected by computed tomography (CT) scan at Screening. Standard of care CT scans completed within 2 weeks prior to Screening may be used in place of the Screening CT scan on a case by-case basis as agreed with the Medical Monitor;
• Prior therapy(ies), if applicable, must be completed according to the criteria below prior to vector administration:
• Cytotoxic chemotherapy, at least 21 days from last dose;
• Non-cytotoxic chemotherapy (e.g., small molecule inhibitor), at least 14 days from last dose;
• Monoclonal antibody, at least 30 days from last dose;
• Non-antibody immunotherapy (e.g., tumor vaccine), at least 42 days from last dose;
• Radiotherapy, at least 14 days from last local site radiotherapy;
• Hematopoietic growth factor, at least 14 days from last dose; or
• Study drug, 30 days or 5 half-lives, whichever is longer, from last dose;

Sponsors & Collaborators

• Ferring Ventures Limited: lead
• University of Pennsylvania: collaborator

Study Sites (29)

University of California, Los Angeles (UCLA) - Medical Center

Los Angeles, California, 90059, United States

Location

University of California, San Francisco (UCSF)

San Francisco, California, 94158, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Marlene & Stewart Greenbaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Masonic Cancer Center - University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Institut Universitaire de Cardiologie et de Pneumologie De Quebec

Québec, Sainte-Foy, G1V 4G5, Canada

Location

Institut Bergonie

Bordeaux, 33076, France

Location

CHRU de Brest - Hopital Augustin Morvan

Brest, 29200, France

Location

CHU de Caen - Hopital Cote de Nacre

Caen, 14033, France

Location

CHRU de Lille

Lille, 59037, France

Location

Institut Curie - Oncologie Medicale

Paris, 75248, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

CHU de Nantes - Hôpital Nord Laennec

Saint-Herblain, 44093, France

Location

Evangelisches Krankenhaus Hamm

Hamm, 59063, Germany

Location

Universitatsklinikum Regensburg

Regensburg, 93053, Germany

Location

Azienda Ospedaliero Universitaria Senese, Cancer Immunotherapy

Siena, Tuscany, 53100, Italy

Location

Med Polonia Sp. z o.o.

Poznan, 60-693, Poland

Location

Centrum Onkologii Instytut im. Marii Sklodowskiej - Curie, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow

Warsaw, ul. Roentgena 5, Poland

Location

Petrov National Medical Research Center of Oncology

Saint Petersburg, 197758, Russia

Location

Volgograd Regional Clinical Oncology Dispensary

Volgograd, 404130, Russia

Location

Derriford Hospital ; Derriford Hospital

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Churchill Hospital

Oxford, Oxford, OX3 7LJ, United Kingdom

Location

Beatson, West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Royal Marsden Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Guy's and St. Thomas' NHS Trust

London, SE1 9RT, United Kingdom

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Gemcitabine; Drug Therapy

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Therapeutics

Limitations and Caveats

At the data cut-off date, treatment with rAd-IFN had not resulted in statistically significant differences from the control group (celecoxib + gemcitabine) in the primary efficacy endpoint (OS) or secondary efficacy endpoints. The study was powered to potentially show statistical significance with 300 patients enrolled. Only 82 patients were screened and 53 were randomised.

Results Point of Contact

• Title: Elisabet Gramming
• Organization: Ferring Pharmaceuticals A/S

elisabet.gramming@ferring.com

+ 45 88 33 88 34

Study Officials

• Daniel Sterman, MD

  NYU Langone Laura and Isaac Perlmutter Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: October 18, 2018
• Study Start: January 21, 2019
• Primary Completion: March 29, 2024
• Study Completion: January 16, 2026
• Last Updated: April 21, 2026
• Results First Posted: May 20, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); PL (2); CA (1); US (7); GB (5); RU (2); FR (7); DE (2); IT (1)