Neoplasms

Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Neoplasm Metastasis

Lymphoma

Melanoma

Lymphoma, Follicular

Mesothelioma

Mesothelioma, Malignant

Primary Myelofibrosis

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Neoplastic Processes

Lymphosarcoma

Follicular Lymphoma

Malignant Mesothelioma

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Pemetrexed

Avelumab

Cisplatin

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antineoplastic Agents, Immunological

Folinic Acid

Folate

Vitamin B9

IOA-244 in combination with pemetrexed/cisplatin/avelumab

IOA-244 will be administered orally once daily (QD)

IOA-244

Avelumab will be administered IV every 2 weeks

Avelumab Injection

Pemetrexed will be administered IV every 3 weeks

Cisplatin will be administered IV every 3 weeks

Ruxolitinib will be administered orally twice a day (BD)

Ruxolitinib

Michael Lahn

The objective of study IOA-244-101 is to determine whether IOA-244 is safe and tolerable in cancer patients (Part A). In addition, the study will assess whether IOA-244 can increase the anti-tumour immune response in patients both as monotherapy and in combination pemetrexed/cisplatin/avelumab (Part B Mesothelioma and NSCLC 1st line), in combination with avelumab (Part B Cutaneous Melanoma and NSCLC 2nd/3rd line) and ruxolitinib (Part B Primary Myelofibrosis)

This is a two-part FIH dose study, where Part A is a dose-escalation group treatment study with IOA-244 and Part B is a parallel cohort study

A Study to Assess a PI3Kδ Inhibitor (IOA-244) in Patients With Metastatic Cancers

First-in-Human Dose Study of IOA-244 Alone and in Combination With Pemetrexed/Cisplatin in Patients With Advanced or Metastatic Cancers

Adverse Events will be assessed by nondirective questioning of the participants during the screening process, at each visit during the study and during the safety follow up period

Time of the maximum observed plasma concentration

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration

Area under the plasma concentration-time curve from time zero extrapolated to infinity

Lymphocytes Immunophenotyping in peripheral blood

Levels of Mesothelin (Mesothelioma participants only)

Percentage of participants with a Complete Response (CR) or Partial Response (PR) RECIST 1.1, for participants with Mesothelioma, modified RECIST and the Lugano 2014 criteria for NHL participants

DOR among patients who achieve objective response as determined by radiographic disease assessment

iOnctura

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gestational Trophoblastic Disease

Trophoblastic Neoplasms

Pregnancy Complications

Pregnancy Complications, Neoplastic

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

Gestational Trophoblastic Tumor

Vasodilator Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Nitroglycerin

Leucovorin

Levoleucovorin

Methotrexate

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Avelumab administration at 800 mg every 2 weeks and methotrexate administration at 1mg/kg/day during 4 months ½ (median)

Avelumab administration at 800mg a 1 hour IV infusion once every 14 days during 4 months ½ (median)

methotrexate administration at 1mg/kg/day during 4 months ½ (median)

Methotrexate 1 GM Injection

Benoit YOU, MD

Laurent VILLENEUVE

Coriolan LEBRETON, MD

Florence JOLY, MD

Cyril ABDEDDAIM

Magali PROVANSAL, MD

Philippe FOLLANA, MD

Jean-Pierre LOTZ, MD

Thibault DE LA MOTTE ROUGE

Laurence Gladieff, Dr

Gestational trophoblastic neoplasias (GTN) are characterized by the persistence of elevated hCG titers after complete uterine evacuation of a partial hydatidiform mole (PHM) or a complete hydatidiform mole.

Low-risk GTN patients (FIGO score ≤ 6) are commonly treated with single agent treatment (methotrexate or actinomycin-D) The cure rate, assessed by hCG normalization, is obtained in 65 to 75% of patients with these agents GTN patients with resistance to these treatments are treated with another single agent drug or polychemotherapy regimens, such as EMA-CO or BEP regimen.

Chemotherapy standard regimens are old and toxic for these young lady patients, with potential long term effects detrimental for further maternity and quality of life

There is a strong rational for investigating the anti-PDL1 monoclonal antibody avelumab in chemoresistant GTN patients. Several elements suggest that the normal pregnancy immune tolerance is "hijacked" by GTN cell for proliferating :

* Spontaneous regressions of metastastic GTN are regularly observed, thereby the role of immune system for rejecting GTN cells.
* Strong and constant overexpression of PDL1 and NK cells has been found in all subtypes and settings of GTN tumors from French reference gestational trophoblastic center.
* Complete and durable responses to pembrolizumab were reported in 3 patients with multi-chemoresistant GTN in United Kingdom.
* Three cases of hCG normalization with avelumab in 6 patients with chemo-resistant GTN enrolled in TROPHIMMUN cohort A (resistant to a mono-chemotherapy).
* Cytotoxicity of avelumab is mediated through antibody dependent cell cytotoxicity (ADCC) by NK cells.

Avelumab and Methotrexate in in Low-risk Gestational Trophoblastic Neoplasias as First Line Treatment

TROPHAMET, a Phase I/II Trial of Avelumab and METhotrexate in Low-risk Gestational TROPHoblastic Neoplasias as First Line Treatment

Safety run-in: dose-limiting toxicities (DLT) will be determined during the first 3 months after the start of treatment

The main endpoint of this study is the rate of patients with successful normalization of hCG allowing for treatment discontinuation (hCG normalization). Patients will continue on treatment until the weekly hCG assays reach the institutional normal threshold, and then for 3 additional cycles, or otherwise will be stopped in the case of resistance, defined as a rise (a \> 20% rise between two assays, observed twice on three consecutive weekly assays) or a plateau (a \< 10% decrease between two assays observed three times on four consecutive weekly assays) in the hCG level, or unacceptable toxicity and/or death.

To assess the rate of treatment-emergent adverse events (TEAEs) and treatment-related adverse events (AEs), treatment-related Grade ≥ 3 AEs, and immune-related AEs, according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)

Resistance rate will be evaluated according to hCG level.

Resistance-free survival will be evaluated according to hCG level.

Relapse-free survival will be evaluated in the case of relapse requiring treatment resumption after a hCG normalization that enabled study treatment discontinuation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Assess a PI3Kδ Inhibitor (IOA-244) in Patients With Metastatic Cancers	NCT04328844	Solid Tumor, Ad... Non-Hodgkin Lym... NSCLC Myelofibrosis Uveal Melanoma	IOA-244 Avelumab Inject... Pemetrexed Cisplatin Ruxolitinib	18 Years -	iOnctura
A Study to Assess a PI3Kδ Inhibitor (IOA-244) in Patients With Metastatic Cancers	NCT04328844	Solid Tumor, Ad... Non-Hodgkin Lym... NSCLC Myelofibrosis Uveal Melanoma	IOA-244 Avelumab Inject... Pemetrexed Cisplatin Ruxolitinib	18 Years -	iOnctura
Avelumab and Methotrexate in in Low-risk Gestational Trophoblastic Neoplasias as First Line Treatment	NCT04396223	Gestational Tro...	Avelumab Inject... Methotrexate 1 ...	18 Years -	Hospices Civils de Lyon

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