Symptoms and General Pathology

All Conditions

Tertiary Lymphoid Structures

Pathological Conditions, Anatomical

All Drugs and Chemicals

Immunomodulating Agents

Participants with TLS+ IO-naïve solid tumors will be treated by MEDI5752

Participants with TLS+ PD1/PDL1-experienced solid tumors will be treated by MEDI5752

A treatment cycle consists of 3 weeks. MEDI5752 will be administered by intravenous infusion at a fixed dose on Day 1 of each cycle

MEDI5752

Antoine ITALIANO, MD, PhD

Simone MATHOULIN-PELISSIER, MD, PhD

Multicentric, prospective, multi-indication, single-treatment arm, open-label phase II trial assessing the efficacy of MEDI5752

Multicentric, prospective, multi-indication, single-treatment arm, open-label phase II trial assessing the efficacy of MEDI5752.

Patients with mature tertiary lymphoid structures advanced solid tumors will be included in two independent cohorts:

* Cohort A: patients with TLS+ IO-naïve solid tumor (miscellaneous)
* Cohort B: patients with TLS+ PD1/PDL1-experienced solid tumor (miscellaneous) Each cohort will rely on a two-stage three-outcome design as described in Sargent et al.

2 independent single-arm, multicenter, phase II trials, based on a two-stage three-outcome design as described in Sargent et al.

Cohort A : patients with TLS+ IO-naïve solid tumor (miscellaneous) Cohort B: patients with TLS+ PD1/PDL1-experienced solid tumor (miscellaneous)

MEDI5752 in Patients With Mature Tertiary Lymphoid Structures Solid Tumors.

A Multicentric Phase II Trial Evaluating MEDI5752 in Patients With Mature Tertiary Lymphoid Structures Solid Tumors.

Antitumor activity will be assessed in terms of objective response rate within 24 weeks based on RECIST v1.1, independently for each cohort, and based on centralized radiological review.

Objective response under treatment is defined as patients with confirmed complete response or confirmed partial response, as per RECIST v1.1, observed during treatment with the investigational product.

Objective response rate is defined as the proportion of patients alive with objective response based on RECIST v1.1.

Objective response is recorded from study treatment initiation until the end of treatment.

CBR is defined as the proportion of patients with clinical benefit at 6 months. Clinical benefit is defined as confirmed complete response, confirmed partial response or stable disease more than 24 weeks, defined as per RECIST v1.1.

BoR is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. The best overall response is determined once all the data for the participant is known (RECIST v1.1).

DoR is defined as the time from documentation of tumor response (complete response/partial response whichever is first recorded) to disease progression, according to RECIST v1.1. DoR will be assessed in responder (confirmed CR / PR) patients only.

PFS is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first

OS is defined as the time from study treatment initiation to death (of any cause)

Number of participants with toxicity graded using the Common Terminology Criteria for Adverse Events version 5

iCBR is defined as the rate of patients with iCR, iPR or immune stable disease (iSD)

iDoR is defined as the time from the date of the first response iCR/iPR (whichever is first recorded) to the date of PD (iUPD confirmed as iCPD) as per iRECIST. iDOR is defined for subjects with iCR or iPR. If a patient has iPR (#1) followed by a iUPD (#1) which is not confirmed, then a iPR (#2) followed by a iUPD (#2) which is confirmed at the next assessment, then the iDOR is calculated from iPR1 until iUPD2

o iPFS is defined as the time from study treatment initiation to the first occurrence of disease progression as per iRECIST or death (of any cause), whichever occurs first. The event date to be used for calculation of progression-free survival (iPFS) should be the first date at which progression criteria are met (ie, the date of iUPD) provided that iCPD is confirmed at the next assessment. If iUPD occurs, but is disregarded because of later iSD, iPR, or iCR, that iUPD date should not be used as the progression event date. If progression is not confirmed and there is no subsequent iSD, iPR, or iCR, then the iUPD date should still be used in the following scenarios: if the patient stops protocol treatment because they were not judged to be clinically stable, or no further response assessments are done (because of patient refusal, protocol noncompliance, or patient death); the next timepoint responses are all iUPD, and iCPD never occurs

iORR is defined as the rate of patients with immune complete or partial responses (iCR, iPR) as per iRECIST. iCR and iPR can be assigned after iUPD (immune unconfirmed progressive disease) has been documented as per iRECIST (Seymour et al)

National Cancer Institute, France

AstraZeneca

Institut Bergonié

Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Pancreatic Neoplasms

Sarcoma

Colorectal Neoplasms

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pancreatic Cancer

Soft Tissue Sarcoma

Antineoplastic Agents

Anti-Infective Agents

Durvalumab

Interferons

Interferon-gamma

Antineoplastic Agents, Immunological

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

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

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

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

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

Tazemetostat

Antoine ITALIANO, MD,PhD

Simone MATHOULIN-PELISSIER, MD,PhD

Jean-Philippe METGES, MD, PhD

Nicolas ISAMBERT, MD, PhD

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

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

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

Combining Epigenetic And Immune Therapy to Beat Cancer.

Combining Epigenetic And Immune Therapy to Beat Cancer. CAIRE Study

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

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

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

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

Objective response is defined as the proportion of patients with complete response (CR) or partial response (PR) observed at 6 months, based on RECIST 1.1 criteria

Best overall response is defined as the best response across all time points (RECIST 1.1). The best overall response is determinded once all the data for the patient is known (RECIST 1.1)

Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST 1.1) or death (from any cause), whichever occurs first

Overall survival is defined as the delay between the start date of treatment and the date of death (of any cause)

Toxicity graded using the Common Terminology Criteria for Adverse Events vers 5

Levels of immune cells in tumors will be measured by immunohistochemistry

Levels of cytokines in blood will be measured by ELISA

Levels of lymphocytes in blood will be measured by flow cytometry

Levels of kynurenin in blood will be measured by ELISA

Epizyme, Inc.

Nivolumab

Relatlimab

Immune Checkpoint Inhibitors

A treatment cycle consists of 4 weeks.

Nivolumab will be administered as a 30-minutes intravenous infusion, on Days 1 and 15 of each cycle (every 2 weeks) - \[240 mg\].

Relatlimab will be administered as a 60-minutes intravenous infusion, on Days 1 and 15 of each cycle (every 2 weeks) - \[80 mg\].

Association of Nivolumab + Relatlimab

A treatment cycle consists of 4 weeks.

Nivolumab will be administered as a 30-minutes intravenous infusion, on Days 1 and 15 of each cycle (every 2 weeks) - \[240 mg\].

Jean-Yves BLAY, MD, PhD

Emmanuelle BOMPAS, MD

Pascaline BOUDOU-ROUQUETTE, MD

Benjamin VERRET, MD

This is a multicenter study assessing the efficacy of nivolumab in association with relatlimab.

This multicenter, prospective, open-labeled 2-arm, randomized non-comparative phase II trial. This phase II trial is based on a 2-stage Simon's optimal design. Randomization 1:1 with 1 patient randomized in experimental arm A (association of nivolumab plus relatlimab) and 1 patient randomized in arm B (treatment by nivolumab alone).

Combination of Nivolumab Plus Relatlimab in Patients With Advanced or Metastatic Soft-tissue Sarcoma: a Proof-of-concept Randomized Phase II Study

Combination of Nivolumab Plus Relatlimab in Patients With Advanced or Metastatic Soft-tissue Sarcoma: a Proof-of-concept Randomized Phase II Study.

Antitumor activity will be assessed in terms of 6-month progression-free rate and is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), based on RECIST 1.1

Best overall response is defined as the best response across all time points (RECIST 1.1). The best overall response is determined once all the data for the patient is known (RECIST 1.1)

GMI is defined for each patient as the ratio of its PFS on the nivolumab + relatlimab treatment combination to its PFS on the previous line of therapy (Von Hoff 1998)

Toxicity graded using the Common Terminology Criteria for Adverse Events version 5

Levels of kynurenine in blood will be measured by ELISA

Levels of immune cells in tumor will be measured by immunohistochemistry

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MEDI5752 in Patients With Mature Tertiary Lymphoid Structures Solid Tumors.	NCT05888857	Advanced Solid ...	MEDI5752	18 Years -	Institut Bergonié
Combining Epigenetic And Immune Therapy to Beat Cancer.	NCT04705818	Advanced Solid ... Advanced Colore... Advanced Soft-t... Advanced Pancre... Adult Solid Tum...	Durvalumab Tazemetostat	18 Years -	Institut Bergonié
Combination of Nivolumab Plus Relatlimab in Patients With Advanced or Metastatic Soft-tissue Sarcoma: a Proof-of-concept Randomized Phase II Study	NCT04095208	Soft Tissue Sar... Advanced Cancer	Association of ... Nivolumab	18 Years -	Institut Bergonié
Combination of Nivolumab Plus Relatlimab in Patients With Advanced or Metastatic Soft-tissue Sarcoma: a Proof-of-concept Randomized Phase II Study	NCT04095208	Soft Tissue Sar... Advanced Cancer	Association of ... Nivolumab	18 Years -	Institut Bergonié

Spots Global Cancer Trial Database for tertiary lymphoid structure