Combining Epigenetic And Immune Therapy to Beat Cancer.

NCT04705818 | Completed Phase 2 DMC

• 2 other identifiers: IB2019-042019-003303-35
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

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

Keywords

tertiary lymphoid structure; pancreatic cancer; soft-tissue sarcoma; immunotherapy; colorectal cancer; solid tumor; epigenetic

Outcome Measures

Primary Outcomes (4)

• Assessment of antitumor activity of durvalumab combined with tazemetostat for cohort A

  Antitumor activity will be assessed in terms of disease control rate, defined as complete response (CR), partial response (PR) and stable disease (SD) as per RECIST v1.1 criteria

  Within 6 months of treatment onset

• Assessment of antitumor activity of durvalumab combined with tazemetostat for cohort B

  Antitumor activity will be assessed in terms of disease control rate, defined as CR, PR and SD as per RECIST v1.1 criteria

  Within 6 months of treatment onset

• Assessment of antitumor activity of durvalumab combined with tazemetostat for cohort C

  Antitumor activity will be assessed in terms of objective response rate, defined as CR and PR as per RECIST v1.1 criteria

  Within 6 months of treatment onset

• Assessment of antitumor activity of durvalumab combined with tazemetostat for cohort D

  Antitumor activity will be assessed in terms of 6-months progression-free rate, defined as CR, PR and SD as per RECIST v1.1 criteria

  6 months

Secondary Outcomes (13)

• Assessment of antitumor activity of durvalumab combined with tazemetostat for cohort D

  Within 6 months of treatment onset

• Assessment of antitumor activity of durvalumab combined with tazemetostat for cohort A

  6 months

• Assessment of antitumor activity of durvalumab combined with tazemetostat for cohort B

  6 months

• Assessment of antitumor activity of durvalumab combined with tazemetostat for cohort C

  6 months

• 6-month objective response (OR) independently for each population

  6 months

Study Arms (4)

Cohort A: pancreatic cancer

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Tazemetostat

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

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Tazemetostat

Cohort C: metastatic solid tumor

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Tazemetostat

Cohort D: soft-tissue sarcoma

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Tazemetostat

Interventions

Durvalumab 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)

Cohort A: pancreatic cancer; Cohort B: not MSI-H or MMR-deficient colorectal cancer; Cohort C: metastatic solid tumor; Cohort D: soft-tissue sarcoma

Tazemetostat 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 A: pancreatic cancer; Cohort B: not MSI-H or MMR-deficient colorectal cancer; Cohort C: metastatic solid tumor; Cohort D: soft-tissue sarcoma

Eligibility Criteria

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

You may qualify if:

• 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).
• 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,
• Advanced disease defined as metastatic or unresectable locally advanced disease,
• Age ≥ 18 years,
• ECOG, Performance status ≤ 1,
• Measurable disease according to RECIST
• Life expectancy \> 3 months,
• 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,
• Adequate hematological, renal, metabolic and hepatic functions
• 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,
• At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
• 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
• 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.
• Voluntary signed and dated written informed consents prior to any specific study procedure,

You may not qualify if:

• Previous treatment with durvalumab or tazemetostat,
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody,
• EGFR/ALK/ROS mutated NSCLC,
• Evidence of progressive or symptomatic central nervous system or leptomeningeal metastases,
• Participation to a study involving a medical or therapeutic intervention in the last 30 days,
• Previous enrolment in the present study,
• Participant unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
• Known hypersensitivity to any involved study drug or of its formulation components,
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
• 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,
• Has known active tuberculosis, hepatitis B or hepatitis C,
• Has a known history of Human Immunodeficiency Virus or known acquired immunodeficiency syndrome,
• Persistent proteinuria \> 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample (≥ Grade 3, NCI-CTCAE v5),
• Non-healing wound, non-healing ulcer, or non-healing bone fracture,
• Participants with evidence or history of any bleeding diathesis, irrespective of severity,

Sponsors & Collaborators

• Institut Bergonié: lead
• AstraZeneca: collaborator
• Epizyme, Inc.: collaborator

Study Sites (3)

Institut Bergonie

Bordeaux, 33076, France

Location

CHRU Brest

Brest, 29200, France

Location

CHU Poitiers

Poitiers, 86000, France

Location

MeSH Terms

Conditions

Tertiary Lymphoid Structures; Pancreatic Neoplasms; Sarcoma; Colorectal Neoplasms

Interventions

durvalumab; tazemetostat

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 4 independant single-arm, phase II trials, based on 2-stage Simon's optimal design: * cohort A: pancreatic cancer * cohort B: not MSI-H or MMR-deficient colorectal cancer * cohort C: metastatic solid tumor with positive interferon gamma signature and/or prensece of tertiary lymphoid structure * cohort D: soft-tissue sarcoma

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: January 12, 2021
• Study Start: July 23, 2021
• Primary Completion: January 7, 2024
• Study Completion: July 17, 2025
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)