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Platinum-refractory Ovarian CarcinomaPhase 1/2PROTANCT05271318

Oncolytic Adenovirus Coding for TNFa and IL2 (TILT-123) With Pembrolizumab or Pembrolizumab (Phase 1a) and Pegylated Liposomal Doxorubicin (Phase 1b) as Treatment for Ovarian Cancer.

A Phase 1/2 study testing TILT-123, pembrolizumab and pegylated liposomal doxorubicin in people with Platinum-refractory Ovarian Carcinoma and Platinum-resistant Ovarian Cancer, run by TILT Biotherapeutics Ltd. at 3 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is an open-label, phase 1/1b, dose-escalation, multicenter and multinational trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with Pembrolizumab, or Pembrolizumab and Pegylated Liposomal Doxorubicin in patients with platinum resistant or refractory ovarian cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
TILT-123, pembrolizumab and pegylated liposomal doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
3 sitesin 2 countries
Study dates
17 May 2022to Aug 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
  • Diagnosis:
  • Phase I part: 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.
  • Phase Ib part: Platinum refractory/resistant ovarian cancer treated with up to one line of prior chemotherapy in refractory/resistant setting. Note: A regimen that contains only one or more biological agents and/or targeted therapies but no cytotoxic drug does not count as a line of chemotherapy Note: For both phase I and phase Ib, 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).
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  • 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.
  • 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 Gilber'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:
  • 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.

Who cannot join

  • 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.
  • Prior therapy:
  • Both phase I and phase Ib parts: 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.
  • Phase Ib part: Prior oncolytic viruses, immune checkpoint inhibitors or anthracyclines (eg. doxorubicin, liposomal doxorubicin, epirubicin or any other anthracycline formulations).
  • 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.
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  • 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.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • Northwell Heatlh/Lenox Hill Hospital

    New York, New York, 10075

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

Finland1 site

  • Docrates Cancer Center

    Helsinki, 00180

Other trials in Finland

About this study

Official title: A Two-part, Phase I/Ib, Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Combination With Pembrolizumab (Phase I Part) and Pembrolizumab and Pegylated Liposomal Doxorubicin (Phase Ib Part) in Patients With Platinum Resistant or Refractory Ovarian Cancer

This is an open-label, phase 1/1b, dose-escalation, multicenter and multinational trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with Pembrolizumab, or Pembrolizumab and Pegylated Liposomal Doxorubicin in patients with platinum resistant or refractory ovarian cancer.

Read the detailed description

This is an open-label, phase 1/1b, dose-escalation, multicenter and multinational trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with Pembrolizumab, or Pembrolizumab and Pegylated Liposomal Doxorubicin in patients with platinum resistant or refractory ovarian cancer. TILT-123 is an oncolytic adenovirus coding for tumor necrosis factor alpha (TNFa) and interleukin 2 (IL-2). Pembrolizumab is a monoclonal antibody binding program cell death 1 (PD-1). Pegylated Liposomal Doxorubicin is a chemotherapy and a pegylated liposomal form of the anthracycline topoisomerase inhibitor, doxorubicin.

Being tested
TILT-123, pembrolizumab, pegylated liposomal doxorubicin
Keywords
Oncolytic virus, Virotherapy, Immune checkpoint inhibitor, Adenovirus, TILT-123, Pembrolizumab, anti-Programmed Cell Death 1 (anti-PD1), Keytruda
Medical subject headings
Adenoviridae Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TILT-123Biological

    Also called Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (TILT-123)

    Tumor necrosis factor alpha (TNFalpha) and Interleukin-2 (IL-2) coding oncolytic adenovirus TILT-123

  • pembrolizumabBiological

    Also called KEYTRUDA®, MK-3475

    pembrolizumab, a monoclonal antibody binding PD-1

  • pegylated liposomal doxorubicinDrug

    Also called PLD

    Pegylated Liposomal Doxorubicin is a chemotherapy and a pegylated liposomal form of the anthracycline topoisomerase inhibitor, doxorubicin.

Study groups in NCT05271318
Study groupRoleWhat they receive
Phase 1 part - TILT-123 and pembrolizumabExperimentalPatients 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.
Receives: Biological: TILT-123; Biological: pembrolizumab
Phase 1b part - TILT-123 and pembrolizumab and pegylated liposomal doxorubicinExperimentalPatients will receive multiple administrations of TILT-123 and pembrolizumab and pegylated liposomal doxorubicin. TILT-123 will be administered at the maximum tolerated dose or maximum feasible dose.
Receives: Biological: TILT-123; Biological: pembrolizumab; Drug: pegylated liposomal doxorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with any (serious and non-serious) Adverse Events

    Measured: Day 92

  2. Number of Participants with vital sign abnormalities

    Measured: Day 92

  3. Number of Participants with abnormal laboratory values

    Measured: Day 92

  4. Number of Participants with Adverse Events assessed by electrocardiograms (ECGs)

    Measured: Day 92

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2022
  2. Study start17 May 2022
  3. Primary completionMar 2027 (estimated)
  4. Study completionAug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05271318
Sponsor's protocol ID
TILT-T563
Other IDs
OC220391, 2021-005083-22, MK-3475-C70, KEYNOTE-C70
Acronym
PROTA
Status last verified
Apr 2026
First submitted
4 Feb 2022
Last updated
5 May 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 33513935

  • 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.

    PubMed 29721366

  • Clubb JHA, Pakola SA, Joenvaara S, Kudling TV, Tohmola T, Arias V, Jirovec E, van der Heijden M, Quixabeira DCA, Pasanen A, Haybout L, Ojala N, Basnet S, Eleuteri A, Ferrero JD, Hirvenoja S, Svane IM, Maenpaa J, Jalkanen K, Block MS, Alanko T, Monberg T, Zahraoui S, Gronberg-Vaha-Koskela S, Salmelin N, Kistler C, Havunen R, Sorsa S, Manuel Dos Santos J, Cervera-Carrascon V, Kanerva A, Hemminki O, Renkonen R, Hemminki A. Dyslipidemia-associated natural IgM improves oncolytic virus TILT-123 efficacy through antibody-dependent enhancement in solid tumors. Mol Ther. 2026 May 6;34(5):3056-3076. doi: 10.1016/j.ymthe.2026.01.019. Epub 2026 Jan 20.

    PubMed 41566775

  • Jirovec E, Quixabeira DCA, Clubb JHA, Pakola SA, Kudling T, Arias V, Haybout L, Jalkanen K, Alanko T, Monberg T, Khammari A, Dreno B, Svane IM, Block MS, Adamo DA, Maenpaa J, Kistler C, Sorsa S, Hemminki O, Kanerva A, Santos JM, Cervera-Carrascon V, Hemminki A. Single intravenous administration of oncolytic adenovirus TILT-123 results in systemic tumor transduction and immune response in patients with advanced solid tumors. J Exp Clin Cancer Res. 2024 Nov 6;43(1):297. doi: 10.1186/s13046-024-03219-0.

    PubMed 39506856

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TILT-123, pembrolizumab and pegylated liposomal doxorubicin in people with Platinum-refractory Ovarian Carcinoma and Platinum-resistant Ovarian Cancer, run by TILT Biotherapeutics Ltd. at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with any (serious and non-serious) Adverse Events (time frame: Day 92). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05271318, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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