Clinical Trials /

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

NCT04328844

Description:

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 with pemetrexed/cisplatin (Part B). Participants will receive IOA-244 for a period of 6 months. After treatment completion, participants will continue in the study for a follow-up period of 6 months.

Related Conditions:
  • Melanoma
  • Mesothelioma
  • Ocular Melanoma
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess a PI3Kδ Inhibitor (IOA-244) in Patients With Metastatic Cancers
  • Official Title: First-in-Human Dose Study of IOA-244 Alone and in Combination With Pemetrexed/Cisplatin in Patients With Advanced or Metastatic Cancers

Clinical Trial IDs

  • ORG STUDY ID: IOA-244-101
  • SECONDARY ID: 2019-000686-20
  • NCT ID: NCT04328844

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
IOA-244Single arm with IOA-244

Purpose

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 with pemetrexed/cisplatin (Part B). Participants will receive IOA-244 for a period of 6 months. After treatment completion, participants will continue in the study for a follow-up period of 6 months.

Trial Arms

NameTypeDescriptionInterventions
Single arm with IOA-244Experimental
  • IOA-244

Eligibility Criteria

        Inclusion Criteria:

          1. ≥18 years of age inclusive, at the time of signing the informed consent

          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          3. Patients with histologically or cytologically confirmed advanced or metastatic
             melanoma (histologically confirmed, unresectable Stage III or IV melanoma),
             mesothelioma or ocular/uveal melanoma

        Exclusion Criteria:

          1. Inability to swallow food or any condition of the upper gastrointestinal tract that
             precludes administration of oral medications

          2. Have prior significant medical history and adverse events (AEs):

               1. History of a prior Grade 3 or 4 immune-related AE (irAE) or any grade ocular irAE
                  from prior immunotherapy

               2. Active autoimmune process (e.g., rheumatoid arthritis, moderate or severe
                  psoriasis, multiple sclerosis, inflammatory bowel disease) (i.e., use of
                  disease-modifying agents, corticosteroids, or immunosuppressive drugs).
                  Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
                  replacement therapy for adrenal or pituitary insufficiency, etc) is not
                  considered a form of systemic treatment

               3. Known active central nervous system (CNS) metastases and/or carcinomatous
                  meningitis Note: Patients with previously treated brain metastases may
                  participate provided they are stable (without evidence of progression by imaging
                  for at least 4 weeks before the first dose of study treatment and any neurologic
                  symptoms have returned to baseline), have no evidence of new or enlarging brain
                  metastases, and have not required steroids for at least 7 days before study
                  treatment

               4. History or presence of an abnormal electrocardiogram (ECG) that, in the
                  Investigator's opinion, is clinically meaningful. Screening QTc interval > 480
                  milliseconds is excluded (corrected by Fridericia). In the event that a single
                  QTc is > 480 milliseconds, the patient may enrol if the average QTc for the 3
                  ECGs is < 480 milliseconds. For patients with an intraventricular conduction
                  delay (QRS interval > 120 msec), the JTc interval may be used in place of the QTc
                  with Sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place
                  of the QTc. Patients with left bundle branch block are excluded Note: QTc
                  prolongation due to pacemaker may enrol if the JT is normal or with Medical
                  Monitor approval

               5. Evidence of interstitial lung disease or active, non-infectious pneumonitis

               6. Active infection requiring systemic therapy

               7. Known additional malignancy that is progressing or requires active treatment
                  Patients with active malignancy requiring concurrent intervention or previous
                  malignancies (except non-melanoma skin cancers, and the following in situ
                  cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma or
                  breast) unless a complete remission was achieved at least 2 years prior to study
                  entry and no additional therapy is required during the study period.

               8. Any serious or uncontrolled medical disorder or active infection that, in the
                  opinion of the Investigator, may increase the risk associated with study
                  participation, study drug administration, or would impair the ability of the
                  patient to receive protocol therapy

          3. Treatment with anticancer medications, investigational drugs, surgery and/or radiation
             within the following interval before the first administration of study drug:

               1. < 14 days for chemotherapy, targeted small-molecule therapy, surgical resection
                  of lesions or radiation therapy (prior palliative radiotherapy must have been
                  completed at least 14 days prior to study drug administration). Patients must
                  also not require corticosteroids and must not have had pneumonitis as a result of
                  treatment. A 1-week washout is permitted for palliative radiation to non-CNS
                  disease with Sponsor approval Note: The use of denosumab is permitted

               2. < 14 days for a prior PD-1 pathway-targeted agent

               3. < 28 days for prior monoclonal antibody used for anticancer therapy with the
                  exception of PD-1 pathway-targeted agents

               4. < 28 days or 5 half-lives (whichever is longer) before the first dose for all
                  other investigational study drugs or devices. For investigational agents with
                  long half-lives (e.g., > 5 days), enrolment before the fifth half-life requires
                  Medical Monitor approval
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Cmax
Time Frame: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
Safety Issue:
Description:Peak Plasma Concentration
Measure:Cmin
Time Frame: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
Safety Issue:
Description:Minimum observed plasma concentration
Measure:
Time Frame: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
Safety Issue:
Description:Terminal elimination half-life
Measure:tmax
Time Frame: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
Safety Issue:
Description:Time of the maximum observed plasma concentration
Measure:AUC0-t
Time Frame: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
Safety Issue:
Description:Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
Measure:AUC0-∞
Time Frame: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
Safety Issue:
Description:Area under the plasma concentration-time curve from time zero extrapolated to infinity
Measure:Pharmacodynamic activity of IOA-244 by determining changes in Lymphocytes counts
Time Frame: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
Safety Issue:
Description:Lymphocytes Immunophenotyping in peripheral blood
Measure:Pharmacodynamic activity of IOA-244 by determining changes in LDH
Time Frame:At Screening (D-28 to D-1), Cycle 1 Day 1, Day 8, Day 15, Day 22 (pre-dose). Each cycle is 28 days
Safety Issue:
Description:Levels of Lactate Dehydrogenase (LDH)
Measure:Pharmacodynamic activity of IOA-244 by evaluating levels of Mesothelin
Time Frame: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
Safety Issue:
Description:Levels of Mesothelin (Mesothelioma participants only)
Measure:Objective Response Rate (ORR)
Time Frame:Up to 28 weeks
Safety Issue:
Description:Percentage of participants with a Complete Response (CR) or Partial Response (PR) RECIST 1.1, or for participants with Mesothelioma, modified RECIST
Measure:Duration of response (DOR)
Time Frame: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
Safety Issue:
Description:DOR among patients who achieve objective response as determined by radiographic disease assessment
Measure:Progression Free Survival (PFS)
Time Frame: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
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From date of the first dose of study treatment until the date of death from any cause, assessed up to 150 weeks
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:iOnctura

Trial Keywords

  • Mesothelioma
  • Melanoma

Last Updated

April 1, 2020