A Safety Study of TMV-018 in Patients With Tumors of the Gastrointestinal Tract

NCT04195373 | Withdrawn Phase 1 DMC

• 1 other identifier: TMV-018-101
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to determine the safety and tolerability of TMV-018 when given alone or in combination with the prodrug 5-Fluorocytosine (5-FC) or an anti-PD-1 checkpoint inhibitor in patients with gastrointestinal tumors. Furthermore, the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018 shall be determined.

Conditions

Gastrointestinal Cancer

Keywords

Colorectal cancer; Esophageal cancer; Gastric cancer; TMV-018; anti-PD-1; 5-FC; oncolytic virus

Outcome Measures

Primary Outcomes (2)

• Frequency of Adverse Events

  Incidence of solicited and unsolicited adverse events from enrollment until end of study.

  4 years

• Determine MTD and dose for phase II

  Determine the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018

  1.5 years

Secondary Outcomes (4)

• Viral replication

  2 years

• Viral distribution

  2 years

• Efficacy of therapy assessed by RECIST 1.1

  4 years

• Efficacy of therapy assessed by changes in tumor marker level

  4 years

Study Arms (3)

TMV-018 + 5-FC

EXPERIMENTAL

Patients will receive intra-tumoral TMV-018 on days 0, 14, 28 and 42, and will be additionally treated with the prodrug 5-FC.

Biological: TMV-018 + 5-FC

TMV-018 + anti-PD-1 inhibitor

EXPERIMENTAL

Patients will receive intra-tumoral TMV-018 on days 0, 14, 28 and 42, and will be additionally treated with an anti-PD-1 Inhibitor.

Biological: TMV-018 + anti-PD-1

TMV-018 + 5-FC + anti-PD-1 inhibitor

EXPERIMENTAL

Patients will receive intra-tumoral TMV-018 on days 0, 14, 28 and 42, and will be additionally treated with the prodrug 5-FC and an anti-PD-1 Inhibitor.

Biological: TMV-018 + 5-FC + anti-PD-1

Interventions

TMV-018 + 5-FC BIOLOGICAL

TMV-018: liquid frozen, life attenuated, oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase"; 1E+06 TCID50 to 1E+08 TCID50 per dose. 5-FC: 150 mg/kg/day for 2 days during each treatment.

TMV-018 + 5-FC

TMV-018 + anti-PD-1 BIOLOGICAL

TMV-018: liquid frozen, life attenuated, oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase"; 1E+06 TCID50 to 1E+08 TCID50 per dose. Anti-PD-1 inhibitor dose according to its SMPC.

TMV-018 + anti-PD-1 inhibitor

TMV-018 + 5-FC + anti-PD-1 BIOLOGICAL

TMV-018: liquid frozen, life attenuated, oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase"; 1E+06 TCID50 to 1E+08 TCID50 per dose. 5-FC: 150 mg/kg/day for 2 days during each treatment cycle. Anti-PD-1 Inhibitor: dose according to its SMPC.

TMV-018 + 5-FC + anti-PD-1 inhibitor

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form must be obtained prior to any research procedures.
• At least 18 years of age on the day of signing the informed consent.
• Histologically confirmed diagnosis of advanced, metastatic tumors of the gastrointestinal tract (stage IV)
• Before enrollment (i.e., at least 4 weeks before study treatment): Prior chemotherapy, targeted therapy, radiotherapy, to treat cancer or major surgery have to be stopped at least 4 weeks prior to enrolment.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and life expectancy ≥ 3 months as assessed during screening period.
• All female participants of childbearing potential, defined as all woman physiologically capable of becoming pregnant, must have a negative pregnancy test at screening.
• Willingness not to become pregnant or to father a child during study participation by practicing reliable methods of contraception.
• Patient must have exhausted all current standard therapy lines in the target cancer indications
• Adequate organ function as determined by laboratory parameters.

You may not qualify if:

• Patients who participated in other studies of anti-tumor therapy within 2 weeks before enrolment.
• Patients with brain metastases.
• Patients with poorly controlled hypertension, or cardiovascular and cerebrovascular diseases with clinical significance.
• Patients with other serious organic diseases or mental disorders.
• Patients with active infections, which cannot be controlled with drugs or have potential impact on treatment, or patients with concurrent opportunistic infections.
• Patients exhibiting evidence of clinically significant immunosuppression such as primary or acquired immunodeficiency state
• Pregnancy (positive pregnancy test at screening or before end of study participation) or lactation at screening or planning to become pregnant before completion of study participation.
• Males who have sex to conceive a child / who want to donate semen, during the study and up to 4 months after the last dose of TMV-018, 5-FC or pembrolizumab.
• Males and female subjects of childbearing potential who are unwilling to use double barrier methods of effective contraception
• Patients with an impaired renal function (creatinine clearance ≤ 40 mL/min).
• Patients currently or recently (\< 2 months) taking fluconazole, itraconazole, clotrimazole troches, itraconazole, amphotericin or other oral anti-fungal medications.
• Patients with contraindications for treatment with flucytosine (5-FC)
• Known hypersensitivity to 5-FU, known deficiency in dihydropyrimidine dehydrogenase (DPD)
• Known hypersensitivity to pembrolizumab, its excipients, or other monoclonal antibody.
• Severe immune-related adverse reactions from treatment with pembrolizumab, defined as any grade 4 toxicity or grade 3 toxicity requiring corticosteroid treatment (\> 10 mg/day prednisone or equivalent) for greater than 12 weeks.

Sponsors & Collaborators

• Themis Bioscience GmbH: lead
• Assign Data Management and Biostatistics GmbH: collaborator
• Optimapharm: collaborator

Study Sites (2)

University Hospital Bonn

Bonn, Germany

Location

University Hospital Tübingen

Tübingen, Germany

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Colorectal Neoplasms; Esophageal Neoplasms; Stomach Neoplasms

Interventions

Flucytosine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ulrich Lauer, MD

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 11, 2019
• Study Start: November 23, 2020
• Primary Completion: November 23, 2020
• Study Completion: November 23, 2020
• Last Updated: November 25, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)