Combining epigenetic and immune therapy to beat cancer

Phase 1

• Conditions: MedDRA version: 21.0Level: LLTClassification code 10033606Term: Pancreatic cancer non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10033605Term: Pancreatic cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10039494Term: Sarcoma NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003303-35-FR
• Lead Sponsor: Institut Bergonié

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-07
• Last Update Posted: 21 May 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Histology: histologically confirmed pancreatic cancer (cohort A), non MSI-H or MMR-deficient colorectal cancer (cohort B), solid tumor with positive IFNG gene expression signature and/or tertiary lymphoid structure positive (cohort C), soft-tissue sarcomas (Cohort D). Other solid tumor types may be included through future amendment of the current version of the study protocol.
2. For cohort C, availability of archived FFPE (Formalin-Fixed Paraffin-Embedded) tumor tissue sample for IFNG gene expression assessment and/or dertermination of the presence of tertiary lymphoid structure,
3. Advanced disease defined as metastatic or unresectable locally advanced disease,
4. Age = 18 years,
5. ECOG, Performance status = 1,
6. Measurable disease according to RECIST
7. Life expectancy > 3 months,
8. Participants must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgment,
9. Adequate hematological, renal, metabolic and hepatic functions,
10. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
11. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
12. Recovery to grade = 1 from any adverse event (AE) derived from previous treatment, excluding alopecia of any grade and non-painful peripheral neuropathy grade = 2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Event - NCI-CTCAE, v5),
13. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to inclusion. Note that pregnancy test must be repeated within 72 hours prior to receiving the first dose of study medication,
14. Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for six months after discontinuation of treatment. Acceptable methods for contraception are described in protocol,
15. Voluntary signed and dated written informed consents prior to any specific study procedure,
16. Participants with a social security in compliance with the French law
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 115
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 58

Exclusion Criteria

1. Previous treatment with durvalumab or tazemetostat,
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways),
3. EGFR/ALK/ROS mutated NSCLC,
4. Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases,
5. Participation to a study involving a medical or therapeutic intervention in the last 30 days,
6. Previous enrolment in the present study,
7. Participant unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
8. Known hypersensitivity to any involved study drug or of its formulation components,
9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
a.Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
b. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses = 10 mg or 10 mg equivalent prednisone per day
c. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable,
10. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment,
11. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan or interstitial lung disease with ongoing signs and symptoms at inclusion. History of radiation pneumonitis in the radiation field (fibrosis) is permitted,
12. Has known active tuberculosis, hepatitis B or hepatitis C,
13. Has a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS),
14. Persistent proteinuria > 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample (= Grade 3, NCI-CTCAE v5),
15. Major surgical procedure or significant traumatic injury within 28 days before inclusion,
16. Non-healing wound, non-healing ulcer, or non-healing bone fracture,
17. Participants with evidence or history of any bleeding diathesis, irrespective of severity,
18. Any hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks prior to inclusion,
19.Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before inclusion (except for adequately treated catheter-related venous thrombosis occurring more than one month before inclusion),
20. Ongoing infection > Grade 2 as per NCI CTCAE v5,
21. Uncontrolled hypertension (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg) despite optimal medical management,
22. Congestive heart failure = New York Heart Association (NHYA) class 2,
23. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months),
24. Myocardial infarction less than 6 months before inclusion,
25. Uncontrolled cardiac arrhythmias,
26. Pregnant or breast-feeding participants,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified