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

TILT Biotherapeutics Ltd.3 sites in 2 countries29 target enrollmentMay 17, 2022

ConditionsPlatinum-refractory Ovarian Carcinoma 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-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

InterventionsTILT-123 pembrolizumab pegylated liposomal doxorubicin

Overview

Phase: Phase 1
Intervention: TILT-123
Conditions: Platinum-refractory Ovarian Carcinoma
Sponsor: TILT Biotherapeutics Ltd.
Enrollment: 29
Locations: 3
Primary Endpoint: Number of Participants with abnormal laboratory values
Status: Recruiting
Last Updated: 6 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

May 17, 2022

End Date

August 1, 2027

Last Updated

6 months ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

TILT Biotherapeutics Ltd.

Responsible Party

Sponsor

Eligibility Criteria

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).
•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).
•The disease burden must be evaluable, but does not need to fulfil RECIST 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 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:

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.
•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.
•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.

Arms & Interventions

Phase 1 part - 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.

Intervention: TILT-123

Phase 1 part - TILT-123 and pembrolizumab

Intervention: pembrolizumab

Phase 1b part - TILT-123 and pembrolizumab and pegylated liposomal doxorubicin

Patients 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.

Intervention: TILT-123

Phase 1b part - TILT-123 and pembrolizumab and pegylated liposomal doxorubicin

Patients 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.

Intervention: pembrolizumab

Phase 1b part - TILT-123 and pembrolizumab and pegylated liposomal doxorubicin

Patients 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.

Intervention: pegylated liposomal doxorubicin