Combining Epigenetic And Immune Therapy to Beat Cancer.

NCT ID: NCT04705818

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 173 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-23
• Study Completion Date: 2027-12-31

Brief Summary

Umbrella study structure to independently and simultaneously assess the effects of the association of durvalumab and tazemetostat in multiple solid tumors.

Detailed Description

4 independant, multicenter, prospective, signle-arm phase II trials, based on 2-stage Simon's optimal design, will be conducted in parallel to assess the efficacy of durvalumab when prescribed with tazemetostat, separately, in distinct cohorts of solid tumors:

• cohort A: patients with pancreatic cancer
• cohort B: patients with colorectal cancer not MSI-H or MMR-deficient
• cohort C: patients with metastatic solid tumors with positive interferon gamma signature and/or tertiary lymphoid structure positive
• cohort D: patients with soft-tissue sarcoma

Conditions

Advanced Solid Tumor; Advanced Colorectal Carcinoma; Advanced Soft-tissue Sarcoma; Advanced Pancreatic Adenocarcinoma; Adult Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: pancreatic cancer

Patients with pancreatic cancer will be treated by durvalumab prescribed in association with tazemetostat

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Durvalumab will be administered by intraveinous infusion (1120 mg) on day 1, every 3 weeks. Treatment by durvalumab will start on Day 22 (i.e., day 1 of cycle 2)

Tazemetostat

Intervention Type: DRUG

Tazemetostat will be administered per-os, twice daily (800 mg x 2), continuously. Treatment by tazemetostat will start on day 1 (of cycle1).

Cohort B: not MSI-H or MMR-deficient colorectal cancer

Patients with colorectal cancer will be treated bydurvalumab prescribed in association with tazemetostat

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Durvalumab will be administered by intraveinous infusion (1120 mg) on day 1, every 3 weeks. Treatment by durvalumab will start on Day 22 (i.e., day 1 of cycle 2)

Tazemetostat

Intervention Type: DRUG

Tazemetostat will be administered per-os, twice daily (800 mg x 2), continuously. Treatment by tazemetostat will start on day 1 (of cycle1).

Cohort C: metastatic solid tumor

Patients with metastatic solid with positive interferon gamma signature and/or presence of tertiary lymphoid structurestumor will be treated bydurvalumab prescribed in association with tazemetostat

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Durvalumab will be administered by intraveinous infusion (1120 mg) on day 1, every 3 weeks. Treatment by durvalumab will start on Day 22 (i.e., day 1 of cycle 2)

Tazemetostat

Intervention Type: DRUG

Tazemetostat will be administered per-os, twice daily (800 mg x 2), continuously. Treatment by tazemetostat will start on day 1 (of cycle1).

Cohort D: soft-tissue sarcoma

Patients with soft-tissue sarcoma will be treated by durvalumab prescribed in association with tazemetostat

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Durvalumab will be administered by intraveinous infusion (1120 mg) on day 1, every 3 weeks. Treatment by durvalumab will start on Day 22 (i.e., day 1 of cycle 2)

Tazemetostat

Intervention Type: DRUG

Tazemetostat will be administered per-os, twice daily (800 mg x 2), continuously. Treatment by tazemetostat will start on day 1 (of cycle1).

Interventions

Durvalumab

Durvalumab will be administered by intraveinous infusion (1120 mg) on day 1, every 3 weeks. Treatment by durvalumab will start on Day 22 (i.e., day 1 of cycle 2)

Intervention Type: DRUG

Tazemetostat

Tazemetostat will be administered per-os, twice daily (800 mg x 2), continuously. Treatment by tazemetostat will start on day 1 (of cycle1).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histology: histologically confirmed solid tumors including 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.

Note: for cohort C, IFNG gene expression and/or presence of tertiary lymphoid structure will be centrally assessed. Cohort D, diagnosis must be confirmed and reviewed by the RRePS Network.as recommended by the French NCI (Inca).

2. For cohort C, availability of archived FFPE tumor tissue sample for IFNG gene expression assessment and/or determination 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. Participant 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

13. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to inclusion.

14. Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for at least nine months after discontinuation of treatment for women and six months after discontinuation of treatment for men.

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.

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 CTLA-4 antibody,

3. EGFR/ALK/ROS mutated NSCLC,

4. Evidence of progressive or symptomatic central nervous system 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

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 or known acquired immunodeficiency syndrome,

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 class 2,

23. Unstable angina, 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,

27. Individuals deprived of liberty or placed under legal guardianship,

28. Prior organ transplantation, including allogeneic stem cell transplantation,

29. Known alcohol or drug abuse,

30. Participants with any condition that impairs their ability to swallow and retain tablets,

31. Other severe acute or chronic medical conditions including immune inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study,

32. Participant with anti-Vitamine K oral anticoagulation therapy,

33. Suspected or known intraabdominal fistula,

34. Screening QTc interval > 480 msec is excluded,

35. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

36. Participants with a prior history of myeloid malignancies, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN),

37. Participants with a prior history of T-cell lymphoblastic lymphoma (T-LBL) / T-cell lymphoblastic leukemia (T-ALL).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Epizyme, Inc.

INDUSTRY

Sponsor Role: collaborator

Institut Bergonié

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut Bergonie

Bordeaux, , France

CHRU Brest

Brest, , France

CHU Poitiers

Poitiers, , France

Countries

France

Other Identifiers

2019-003303-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IB2019-04

Identifier Type: -

Identifier Source: org_study_id