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Solid Tumor, AdultPhase 1NCT04328844

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

A Phase 1 study testing IOA-244, Avelumab Injection and Pemetrexed in people with Solid Tumor, Adult and Non-Hodgkin Lymphoma, Adult, run by iOnctura at 3 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
IOA-244, Avelumab Injection and Pemetrexed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
210 participants
Where
3 sitesin 2 countries
Study dates
25 Feb 2020to Mar 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥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.
Show all 64Show fewer
  • 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.
  • Part B: Considered for first-line treatment with pemetrexed/cisplatin and avelumab.
  • For Patients with Indolent Non-Hodgkin Lymphoma, type Follicular Lymphoma (FL):
  • Patients must have a past diagnosis of indolent Non-Hodgkin lymphoma, type Follicular Lymphoma, Grade 1-3A.(Dreyling et al., 2016)
  • Patients must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy, such as rituximab monotherapy, chemotherapy given with or without rituximab, radioimmunoconjugates (e.g., 90Y-ibritumomab tiuxetan and 131I-tositumomab).
  • Must have documented relapsed, refractory, or PD after treatment with systemic therapy (refractory defined as less than PR or disease progression <6 months after last dose).
  • Patients with prior exposure to a PI3K inhibitor (e.g., idelalisib/GS-1101, duvelisib) or a Bruton's tyrosine kinase (BTK) inhibitor are eligible if they discontinued either inhibitors in the last 4 weeks prior entering study treatment.
  • Patients are not eligible for transplantation (autologous or any similar intervention, including CART-cell therapy).
  • For Patients with Non-Hodgkin Lymphoma, type Peripheral T cell lymphoma (PTCL):
  • Diagnosis of one of the following histologic subtypes of PTCL, pathologically-confirmed, as defined by the World Health Organization (other rare PTCL may be enrolled upon discussion with the medical monitor of this study):
  • Peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS)
  • Angioimmunoblastic T-cell lymphomas (AITL)
  • Anaplastic large cell lymphoma (ALCL)
  • Natural-killer/T-cell lymphoma (NKTL)
  • Received at least 2 cycles of one prior regimen administered with curative intent and one of the following:
  • failed to achieve at least a partial response after 2 or more cycles;
  • failed to achieve a complete response after 6 or more cycles; and/or
  • progressed after an initial response.
  • For patients with CD30+ ALCL, failed or are ineligible or intolerant to brentuximab vedotin.
  • Measurable disease as defined by IWG for PTCL, i.e., at least 1 measurable disease lesion > 1.5 cm in at least one dimension by 18FDG-PET-CT, MRI, or diagnostic CT.
  • Patients with prior exposure to a PI3K inhibitor (e.g., idelalisib/GS-1101, duvelisib) or a Bruton's tyrosine kinase (BTK) inhibitor are eligible if they discontinued either inhibitors in the last 4 weeks prior entering study treatment.
  • For Patients with Non-Small Cell Lung Cancer (NSCLC) 1st line:
  • Histological diagnosis of locally advanced (primary or recurrent) NSCLC non-squamous not amenable for treatment with curative intent.
  • No prior systemic treatment for unresectable locally advanced or metastatic disease for NSCLC.
  • Non-squamous NSCLC, with no activating EGFR mutations, ALK or ROS1 translocations/rearrangements.
  • If monotherapy pembrolizumab is available as a standard of care treatment option, patients must have a tumour proportion score (TPS) <50% for PD-L1 (e.g., via the 22C3 pharmDx or the Ventana (SP263) PD-L1 IHC assay, or any other approved IHC assay.
  • For Patients with Non-Small Cell Lung Cancer (NSCLC) 2nd or 3rd line:
  • Histological confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression.
  • Considered for 2nd line or 3rd line treatment either after radiographic progression or on stable disease:
  • Participants must have progressed after a minimum of 2 cycles of 1 course of a platinum based combination therapy administered for the treatment of a metastatic disease.
  • For Patients with Primary Myelofibrosis (PMF):
  • Diagnosis of PMF, Post-Polycythemia Vera Myelofibrosis MF(PPV-MF), or post-essential thrombocythemia MF (PET-MF)
  • Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-1, intermediate-2, or high.
  • Treated with ruxolitinib for ≥ 3 months with a stable dose for at least the last 8 weeks prior to Day 1 and no significant spleen reduction (e.g., less than 15% spleen size reduction, or corresponding lack of response in spleen volume).
  • Did not receive experimental drug therapy for MF or any other drug considered as an effective treatment for MF (eg, danazol, hydroxyurea, interferon products) within the last 2 months prior to starting study treatment.
  • Splenic irradiation within 6 months before receiving the first dose of study drug.
  • Independent of spleen size. active symptoms of MF at the screening visit, as demonstrated by the presence of a Total Symptom Score (TSS) of ≥ 10 using the Screening Symptom Form.
  • Screening bone marrow biopsy specimen and pathology report(s) available that was obtained no more than 2 months prior to starting the study treatment or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks thereafter. Screening/baseline biopsy specimen must show diagnosis of MF.
  • Peripheral blast count < 10%.
  • Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug or anticipated during the study.
  • Presence of measurable disease per RECIST v.1.1, or mRECIST (for cohort with pleural mesothelioma patients), as determined by the site study team. Tumour lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • For NHL (FL and PTCL) patients: Have measurable disease as defined by the Lugano Classification, including at least one lymph node or tumour mass greater than or equal to 1.5 cm.
  • For PMF patients: Have measurable disease as defined by IWG-MRT criteria.
  • For patients with prior systemic therapies (Groups 1, 2, 6, and 7) disease progression must be reported after available therapies for advanced or metastatic disease that are known to confer clinical benefit, been intolerant to treatment, or refused standard treatment. Within 6 months and prior to entering the study, a patient who has completed an adjuvant, neo-adjuvant, or chemo-radiation regimens would be considered of having received 1 prior systemic regimen and would not require an additional systemic regimen for advanced or metastatic disease.
  • Willingness to undergo a pre-treatment and on-treatment tumour biopsy to obtain the specimen (for NHL and PMF: see respective requirements).
  • Note: If a patient has signed the informed consent and is scheduled to have a tumour biopsy for the purposes of this study, and it is subsequently determined that tumour tissue cannot safely be obtained, the patient may still enrol in the study, and the patient may be replaced, if enrolled in Part A, after discussion between the Sponsor and Investigator. The patient will be replaced if enrolled in Part B. However, all patients will be part of the final safety PK, PD (except for the examinations related to the pre- and post-dosing biopsy) and efficacy evaluation.
  • Willingness to avoid pregnancy or fathering children based on the criteria below:
  • Women of non-childbearing potential (i.e., surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age).
  • Women of childbearing potential who had a negative serum pregnancy test at screening and who agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up, at least 1 month after the last dose of study treatment. Women receiving cisplatin should not become pregnant for at least 6 months after receiving the last dose of cisplatin. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the patient and their understanding confirmed.
  • Men who agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow-up, at least 1 month after the last dose of study treatment. Men receiving pemetrexed and/or cisplatin should not father within 6 months of last treatment with pemetrexed and/or cisplatin. Permitted methods that are at least 99% effective in preventing pregnancy (see should be communicated to the patient and their understanding confirmed.

Who cannot join

None listed.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Italy2 sites

  • Humanitas Research Hospital

    Rozzano, Milan, 20089

  • Medical Oncology and Immunotherapy Unit, University Hospital of Siena

    Siena, 53100

Other trials in Italy

United Kingdom1 site

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

Other trials in United Kingdom

About this study

Official title: First-in-Human Dose Study of IOA-244 in Patients With Advanced or Metastatic Cancers

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)

Being tested
IOA-244, Avelumab Injection, Pemetrexed, Cisplatin, Ruxolitinib
Keywords
Mesothelioma, Melanoma, Follicular Lymphoma, NSCLC, Uveal Melanoma, Myelofibrosis, PTCL
Medical subject headings
Lymphoma, Non-Hodgkin, Primary Myelofibrosis, Uveal Melanoma, Mesothelioma, Melanoma, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IOA-244Drug

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

  • Avelumab InjectionDrug

    Avelumab will be administered IV every 2 weeks

  • PemetrexedDrug

    Pemetrexed will be administered IV every 3 weeks

  • CisplatinDrug

    Cisplatin will be administered IV every 3 weeks

  • RuxolitinibDrug

    Ruxolitinib will be administered orally twice a day (BD)

Study groups in NCT04328844
Study groupRoleWhat they receive
Group 1: Cutaneous MelanomaExperimentalIOA-244 in combination with avelumab
Receives: Drug: IOA-244; Drug: Avelumab Injection
Group 2: Uveal MelanomaExperimentalIOA-244 as monotherapy
Receives: Drug: IOA-244
Group 3: MyelofibrosisExperimentalIOA-244 in combination with ruxolitinib
Receives: Drug: IOA-244; Drug: Ruxolitinib
Group 4: MesotheliomaExperimentalIOA-244 in combination with pemetrexed/cisplatin/avelumab
Receives: Drug: IOA-244; Drug: Avelumab Injection; Drug: Pemetrexed; Drug: Cisplatin
Group 5: NSCLC 1st lineExperimentalIOA-244 in combination with pemetrexed/cisplatin/avelumab
Receives: Drug: IOA-244; Drug: Avelumab Injection; Drug: Pemetrexed; Drug: Cisplatin
Group 6: NSCLC 2nd/3rd lineExperimentalIOA-244 in combination with avelumab
Receives: Drug: IOA-244; Drug: Avelumab Injection
Group 7: NHL-FL and NHL-PTCLExperimentalIOA-244 as monotherapy
Receives: Drug: IOA-244

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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)

  1. Cmax

    Peak Plasma Concentration

    Measured: 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

  2. Cmin

    Minimum observed plasma concentration

    Measured: 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

  3. t½

    Terminal elimination half-life

    Measured: 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

  4. tmax

    Time of the maximum observed plasma concentration

    Measured: 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

  5. AUC0-t

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

    Measured: 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

  6. AUC0-∞

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

    Measured: 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

  7. Pharmacodynamic activity of IOA-244 by determining changes in Lymphocytes counts

    Lymphocytes Immunophenotyping in peripheral blood

    Measured: At Cycle 1 Day 1, Day 2, Day 15 (pre-dose), From Cycle 2 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days

  8. Pharmacodynamic activity of IOA-244 by determining changes in LDH

    Levels of Lactate Dehydrogenase (LDH)

    Measured: At Screening (D-28 to D-1), Cycle 1 Day 1, Day 8, Day 15, Day 22 (pre-dose). Each cycle is 28 days

  9. Pharmacodynamic activity of IOA-244 by evaluating levels of Mesothelin

    Levels of Mesothelin (Mesothelioma participants only)

    Measured: At Cycle 1, Day 1 and Day 15 (pre-dose) , From Cycle 2 to Cycle 6, Day 1 (pre-dose). Each cycle is 28 days

  10. Objective Response Rate (ORR)

    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

    Measured: Up to 28 weeks

  11. Duration of response (DOR)

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

    Measured: From date of the first documented evidence of CR or PR until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 54 weeks

  12. Progression Free Survival (PFS)

    Measured: From date of the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 104 weeks

  13. Overall Survival (OS)

    Measured: From date of the first dose of study treatment until the date of death from any cause, assessed up to 150 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2020
  2. Study start25 Feb 2020
  3. Primary completion13 Dec 2023
  4. Study completionMar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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
Masking
None (open label)
Enrolment
210 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04328844
Sponsor's protocol ID
IOA-244-101
Other IDs
2019-000686-20, 2019
Status last verified
Jul 2026
First submitted
11 Mar 2020
Last updated
8 Jul 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Di Giacomo AM, Simonelli M, Losurdo A, Spiliopoulou P, D'Alonzo V, Amato G, Valente M, Barcenilla H, Johnsson A, Gonzalez L, Tan Z, Tadepally L, Brodin P, Lahn M, Di Conza G, Zorrilla R, van der Veen L, Bevilacqua A, Kaur P, Hammett T, Durini M, Corsi A, Sindhwani N, Occhipinti M, Snijder R, Abdul-Ahad A, Meijer A, Postiglione U, Price G, Hopton G, Wood E, Vuaroqueaux V, Peille AL, Graham J, Poi M, Spetzler D, Carlo-Stella C, Santoro A, Evans TRJ, Maio M. The conformation-selective PI3Kdelta inhibitor roginolisib in patients with advanced or metastatic cancer, including metastatic uveal melanoma: first-in-human clinical trial. Nat Commun. 2026 Oct 9;17(1):10219. doi: 10.1038/s41467-026-77358-7.

    PubMed 42855460

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IOA-244, Avelumab Injection and Pemetrexed in people with Solid Tumor, Adult and Non-Hodgkin Lymphoma, Adult, run by iOnctura at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 64 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Numbers of participants with treatment-related adverse events as assessed by CTCAE v5.0 (time frame: From time of first drug administration to first documented progression, toxicity or death from any cause whichever occurs first, assessed at week 30). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04328844, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.

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