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

NCT04328844 | Active Not Recruiting Phase 1

• 2 other identifiers: IOA-244-1012019-000686-20
• Study Type: interventional
• Target: 210
• Locations: 2 countries
• Sites: 3

Brief Summary

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)

Conditions

Non-Hodgkin Lymphoma, Adult; NSCLC; Myelofibrosis; Uveal Melanoma; Solid Tumor, Adult

Keywords

Mesothelioma; Melanoma; Follicular Lymphoma; NSCLC; Uveal Melanoma; Myelofibrosis; PTCL

Outcome Measures

Primary Outcomes (1)

• Numbers of participants with treatment-related adverse events as assessed by CTCAE v5.0

  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

  From time of first drug administration to first documented progression, toxicity or death from any cause whichever occurs first, assessed at week 30

Secondary Outcomes (13)

• Cmax

  At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days

• Cmin

  At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days

• t½

  At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days

• tmax

  At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days

• AUC0-t

  At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days

Study Arms (7)

Group 1: Cutaneous Melanoma

EXPERIMENTAL

IOA-244 in combination with avelumab

Drug: IOA-244; Drug: Avelumab Injection

Group 2: Uveal Melanoma

EXPERIMENTAL

IOA-244 as monotherapy

Drug: IOA-244

Group 3: Myelofibrosis

EXPERIMENTAL

IOA-244 in combination with ruxolitinib

Drug: IOA-244; Drug: Ruxolitinib

Group 4: Mesothelioma

EXPERIMENTAL

IOA-244 in combination with pemetrexed/cisplatin/avelumab

Drug: IOA-244; Drug: Avelumab Injection; Drug: Pemetrexed; Drug: Cisplatin

Group 5: NSCLC 1st line

EXPERIMENTAL

IOA-244 in combination with pemetrexed/cisplatin/avelumab

Drug: IOA-244; Drug: Avelumab Injection; Drug: Pemetrexed; Drug: Cisplatin

Group 6: NSCLC 2nd/3rd line

EXPERIMENTAL

IOA-244 in combination with avelumab

Drug: IOA-244; Drug: Avelumab Injection

Group 7: NHL-FL and NHL-PTCL

EXPERIMENTAL

IOA-244 as monotherapy

Drug: IOA-244

Interventions

Cisplatin DRUG

Cisplatin will be administered IV every 3 weeks

Group 4: Mesothelioma; Group 5: NSCLC 1st line

Ruxolitinib DRUG

Ruxolitinib will be administered orally twice a day (BD)

Group 3: Myelofibrosis

IOA-244 DRUG

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

Group 1: Cutaneous Melanoma; Group 2: Uveal Melanoma; Group 3: Myelofibrosis; Group 4: Mesothelioma; Group 5: NSCLC 1st line; Group 6: NSCLC 2nd/3rd line; Group 7: NHL-FL and NHL-PTCL

Avelumab Injection DRUG

Avelumab will be administered IV every 2 weeks

Group 1: Cutaneous Melanoma; Group 4: Mesothelioma; Group 5: NSCLC 1st line; Group 6: NSCLC 2nd/3rd line

Pemetrexed DRUG

Pemetrexed will be administered IV every 3 weeks

Group 4: Mesothelioma; Group 5: NSCLC 1st line

Eligibility Criteria

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

You may qualify if:

• ≥18 years of age inclusive, at the time of signing the informed consent.
• Capable of giving signed informed consent, which includes compliance with the requirements of this protocol.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. For patients with NHL, ECOG 2 will be allowed.
• Patients with histologically or cytologically confirmed advanced or metastatic malignancies (including histologically confirmed, unresectable Stage III or IV melanoma); see following details for each malignancy:
• For Patients with cutaneous and mucosal melanoma:
• Baseline lactate dehydrogenase levels are available.
• Disease progression is confirmed and they are eligible for second- or third-line treatment:
• After first-line treatment and progression on approved programmed cell death-1 (PD-1) or cytotoxic T lymphocyte antigen-4 (CTLA-4) or combination of PD-1 and CTLA-4-pathway targeted agent.
• After second-line treatment and progression on prior BRAF V600 mutation targeted agent followed by PD-1 or CTLA-4-pathway targeted agent (Note: There is no mandatory sequence of these approved treatments).
• No clinically significant tumour-related symptoms.
• For Patients with metastatic ocular/uveal melanoma:
• Patients must have metastatic histologically or cytologically confirmed uveal melanoma.
• For Patients with advanced or metastatic mesothelioma:
• Histological confirmation of mesothelioma (any subtype).
• Part A: They received at least one prior line of treatment (including patients who were re-challenged with pemetrexed-based therapy). Prior maintenance therapy is permitted but will not count as a line of treatment.

Sponsors & Collaborators

• iOnctura: lead

Study Sites (3)

Humanitas Research Hospital

Rozzano, Milan, 20089, Italy

Location

Medical Oncology and Immunotherapy Unit, University Hospital of Siena

Siena, 53100, Italy

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Primary Myelofibrosis; Uveal Melanoma; Mesothelioma; Melanoma; Lymphoma, Follicular

Interventions

avelumab; Pemetrexed; Cisplatin; ruxolitinib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Michael Lahn

  iOnctura

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 11, 2020
• First Posted: March 31, 2020
• Study Start: February 25, 2020
• Primary Completion: December 13, 2023
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); GB (1)