- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05271318
Oncolytic Adenovirus TILT-123 With Pembrolizumab as Treatment for Ovarian Cancer (PROTA)
A Phase I Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Combination With Pembrolizumab in Patients With Platinum Resistant or Refractory Ovarian Cancer
Study Overview
Status
Conditions
- Platinum-resistant Ovarian Cancer
- Platinum-Resistant Fallopian Tube Carcinoma
- Platinum-Resistant Primary Peritoneal Carcinoma
- Platinum-Refractory Fallopian Tube Carcinoma
- Platinum-Refractory Primary Peritoneal Carcinoma
- Platinum-refractory Ovarian Carcinoma
- Platinum-Sensitive Ovarian Cancer in Which the Participant Has Allergy or Severe Intolerance to Carboplatin and/or Cisplatin
- Platinum-Sensitive Fallopian Tube Carcinoma in Which the Participant Has Allergy or Severe Intolerance to Carboplatin and/or Cisplatin
- Platinum-Sensitive Primary Peritoneal Carcinoma in Which the Participant Has Allergy or Severe Intolerance to Carboplatin and/or Cisplatin
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: TILT Trials
- Phone Number: +358 509181 580
- Email: trials@tiltbio.com
Study Locations
-
-
-
Helsinki, Finland, 00180
- Recruiting
- Docrates Cancer Center
-
Contact:
- Johanna Mäenpää, MD, PhD
- Phone Number: +358 107732050
- Email: hospital@docrates.com
-
Principal Investigator:
- Johanna Mäenpää
-
-
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Recruiting
- Mayo Clinic
-
Contact:
- Matthew S. Block, MD, PhD
-
Principal Investigator:
- Matthew S. Block, MD, PhD
-
-
New York
-
New York, New York, United States, 10075
- Recruiting
- Northwell Heatlh/Lenox Hill Hospital
-
Contact:
- Jeannine Villella, DO
-
Principal Investigator:
- Jeannine Villella, DO
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Signed and dated informed consent(s) by the participant or legal representative before any trial-related activities.
- Female over 18 years of age on day of signing informed consent(s).
- Histologically confirmed ovarian cancer (including fallopian tube and primary peritoneal cancer) resistant to platinum (defined as progression of cancer within 183 days of the most recent dose of cisplatin or carboplatin) or refractory to platinum (defined as progression of cancer within 30 days of the most recent dose of cisplatin or carboplatin) ovarian cancer, which cannot be treated with curative intent with available therapies. Note: Poly(ADP)-ribose polymerase (PARP) inhibitors should be considered as indicated in clinical practice, prior to trial enrollment. Patients who have platinum-sensitive disease (no recurrence or progression within 183 days of the last dose of platinum-containing chemotherapy) but who have an allergy or severe intolerance to carboplatin and/or cisplatin may be included.
- At least one tumor (>14 mm in diameter) or carcinomatosis must be available for local virus injection (intratumoral and/or intraperitoneal).
- The disease burden must be evaluable, but does not need to fulfil RECIST 1.1.
Have adequate organ function as defined in the following values below. Specimens must be collected within 10 days prior to the start of study treatment.
a. Hematological laboratory values i. Absolute neutrophil count (ANC): ≥1500/µL ii. Platelets: ≥ 100 000/µL iii. Hemoglobin: ≥9.0 g/dL or ≥5.6 mmol/L. Criteria must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin (≥ approximately 3 months. iv. Leukocytes (WBC) > 3.0x10^9/L b. Renal laboratory values i. Glomerular Filtration Rate (GFR): >45 ml/min (CKD-EPI formula). c. Hepatic laboratory values i. Total bilirubin: ≤1.5 × Upper Limit of Normal (ULN) OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN (excluding patients with Gilbert's Disease) ii. Aspartate Aminotransferase (AST) (SGOT) and Alanine Aminotransferase (ALT) (SGPT): ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
Patients must be willing to use adequate forms of contraception from screening, during the trial, and for a minimum of 120 days after end of treatment, in accordance with the following:
i. Women of childbearing potential: Barrier contraceptive method (i.e. condom) must be used in addition to one of the following methods: Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections). ii. Women not of childbearing potential: Barrier contraceptive method (i.e. condom) must be used.
- Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance score of 0-1 at screening.
- Life expectancy longer than 3 months.
- Capable of understanding and complying with parameters as outlined in the protocol.
Exclusion Criteria:
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) and inhaled and topical treatments are not considered a form of systemic treatment and are allowed.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
- Treated with any anti-cancer therapy within 30 days prior to the first virus injection. Anti-cancer therapy is defined as anti-cancer agents (e.g. surgery, chemotherapy, immune-checkpoint inhibitors, kinase inhibitors, PARP inhibitors, biological therapies, hormonal therapies, radiation, etc.). Continuation of hormonal therapy or use of bone modifying agents (e.g. bisphosphonate or denosumab) is allowed if started at least 3 months before.
- Participants must have recovered from all Adverse Events (AE)s due to previous therapies to ≤Grade 1or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible. If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
- Treated with a prior radiotherapy, including for palliative purposes, within 2 weeks of start of study treatment (before or after). Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-Central Nervous System (CNS) disease. Palliative radiation is allowed from day 15 during the trial treatment period, if deemed necessary by the investigator.
- Treated with a prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., Cytotoxic T lymphocyte-associated Antigen (CTLA)-4, Tumor necrosis factor receptor superfamily, member 4 (OX40), CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related Adverse Events (irAE).
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 30 days prior to the first virus injection. An investigational agent is any drug or therapy that is currently not approved for use in humans. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Uncontrolled cardiac or vascular diseases.
- History of myocardial infarction or cerebral stroke within the previous 12 months before screening or is not sufficiently recovered from an older infarction or cerebral stroke.
- History of severe hepatic dysfunction.
- History of hepatitis B (defined as HBsAg reactive), Hepatitis C (defined as hepatitis C virus (HCV) RNA [qualitative] is detected) and/or HIV. No testing for Hepatitis B, Hepatitis C and HIV is required unless mandated by a local health authority.
- History of coagulation disorder.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Female patients who are pregnant, breastfeeding or intend to become pregnant. Women of childbearing potential who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 3 months by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
- Has an active infection requiring systemic therapy.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Allergy to ingredients present in the investigational medicinal products (ingredients are listed in the protocol) ie. severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Known contraindications to pembrolizumab.
- Has had an allogenic tissue/solid organ transplant.
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines are allowed.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TILT-123 and pembrolizumab
Patients will receive multiple administrations of TILT-123 and pembrolizumab. Escalation to the next dose of TILT-123 level will occur when the safety data has been evaluated for all patients in the preceding dose level. |
Tumor necrosis factor alpha (TNFalpha) and Interleukin-2 (IL-2) coding oncolytic adenovirus TILT-123
Other Names:
pembrolizumab, a monoclonal antibody binding PD-1
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of Participants with any (serious and non-serious) Adverse Events
Time Frame: Day 92
|
Day 92
|
Number of Participants with vital sign abnormalities
Time Frame: Day 92
|
Day 92
|
Number of Participants with abnormal laboratory values
Time Frame: Day 92
|
Day 92
|
Number of Participants with Adverse Events assessed by electrocardiograms (ECGs)
Time Frame: Day 92
|
Day 92
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Havunen R, Kalliokoski R, Siurala M, Sorsa S, Santos JM, Cervera-Carrascon V, Anttila M, Hemminki A. Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1. Cells. 2021 Jan 27;10(2):246. doi: 10.3390/cells10020246.
- Cervera-Carrascon V, Siurala M, Santos JM, Havunen R, Tahtinen S, Karell P, Sorsa S, Kanerva A, Hemminki A. TNFa and IL-2 armed adenoviruses enable complete responses by anti-PD-1 checkpoint blockade. Oncoimmunology. 2018 Apr 9;7(5):e1412902. doi: 10.1080/2162402X.2017.1412902. eCollection 2018.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- DNA Virus Infections
- Fallopian Tube Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Hypersensitivity
- Carcinoma
- Ovarian Neoplasms
- Fallopian Tube Neoplasms
- Carcinoma, Ovarian Epithelial
- Adenoviridae Infections
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- TILT-T563
- OC220391 (Other Grant/Funding Number: US Department of Defense)
- 2021-005083-22 (EudraCT Number)
- MK-3475-C70 (Other Identifier: Merck Sharp & Dohme LLC)
- KEYNOTE-C70 (Other Identifier: Merck Sharp & Dohme LLC)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Platinum-resistant Ovarian Cancer
-
Aduro Biotech, Inc.Incyte CorporationTerminatedPlatinum-resistant Ovarian Cancer | Platinum-resistant Fallopian Cancer | Platinum-resistant Peritoneal CancerUnited States, Canada
-
Seoul National University HospitalPharos iBio Co., Ltd.RecruitingPlatinum-resistant Ovarian Cancer | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-refractory Ovarian CarcinomaKorea, Republic of
-
Vascular Biogenics Ltd. operating as VBL TherapeuticsCompletedPlatinum Resistant Ovarian CancerUnited States
-
Shattuck Labs, Inc.Enrolling by invitationOvarian Cancer | Fallopian Tube Cancer | Epithelial Ovarian Cancer | Platinum-resistant Ovarian Cancer | Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal CarcinomaUnited States, United Kingdom, Spain, Canada
-
Xennials Therapeutics Australia Pty LtdPinotbio, Inc.TerminatedAdvanced Solid Tumor | High-grade Glioma | Platinum-Resistant Ovarian Cancer | Platinum-Resistant Urothelial CarcinomaAustralia
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingPlatinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Stage IV Fallopian Tube Cancer AJCC v8 | Stage IV Ovarian Cancer AJCC v8 | Stage IV Primary Peritoneal Cancer AJCC v8United States
-
Nuvation Bio Inc.RecruitingPancreatic Cancer | Advanced Solid Tumor | HER2-negative Breast Cancer | Metastatic Castration-resistant Prostate Cancer (mCRPC) | Platinum-resistant Ovarian Cancer (PROC)United States
-
Mersana TherapeuticsIQVIA Biotech; PSI CRORecruitingPlatinum Resistant Ovarian Cancer | Non Small Cell Lung Cancer MetastaticUnited States, Spain, United Kingdom, Australia, France, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, Finland, Hungary, Italy, Lithuania, New Zealand, Norway, Poland, Sweden
-
Roswell Park Cancer InstituteActive, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Platinum-Sensitive Ovarian Carcinoma | Refractory Ovarian... and other conditionsUnited States
-
OncoResponse, Inc.RecruitingCancer | Metastatic Cancer | Advanced Solid Tumor | Platinum-resistant Ovarian Cancer | Malignant Neoplasm | Tumor, Solid | Cutaneous Squamous Cell CarcinomaUnited States
Clinical Trials on TILT-123
-
TILT Biotherapeutics Ltd.Active, not recruitingMetastatic MelanomaFrance, Denmark
-
TILT Biotherapeutics Ltd.Recruiting
-
TILT Biotherapeutics Ltd.RecruitingMelanoma | Head and Neck Squamous Cell CarcinomaUnited States, Finland
-
TILT Biotherapeutics Ltd.Merck Sharp & Dohme LLCRecruitingLung CancerUnited States
-
Seoul National University HospitalUnknownCatheterization | Posture
-
Institute for Neurodegenerative DisordersTerminatedAlzheimer's DiseaseUnited States
-
Molecular Insight Pharmaceuticals, Inc.Completed
-
Bausch Health Americas, Inc.CompletedAcne VulgarisUnited States, Canada
-
Bausch Health Americas, Inc.CompletedAcne VulgarisUnited States, Canada
-
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityNot yet recruitingCritically Ill | Mechanical Ventilation | Early Mobilization | Diaphragm Dysfunction