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

• Status: Recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

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 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: iOnctura

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, ocular/uveal melanoma or NHL

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. For patients with NHL ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic steroids > 20 mg prednisone (or equivalent) QD.

3. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. For NHL patients, known central nervous system (CNS) lymphoma or leukemia: subjects with symptoms of CNS disease must have a negative CT scan or negative diagnostic lumbar puncture prior to randomization.

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. For patients with NHL:

• History of tuberculosis treatment within the preceding two years

• Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment (defined as requiring intravenous [IV] antimicrobial, antifungal or antiviral agents). Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met and there is no evidence of active infection at randomization

• Human immunodeficiency virus (HIV) infection

• Prior, current or chronic hepatitis B or hepatitis C infection

• Unable to receive prophylactic treatment for pneumocystis or herpes simplex virus (HSV)

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. For patients with NHL:

• Clinical or laboratory evidence of transformation to an aggressive subtype.

• Autoimmune haemolytic anaemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) that is uncontrolled or requiring > 20 mg once daily (QD) of prednisone (or equivalent) to maintain haemoglobin > 8.0 g/dL or platelets > 10x109/L without transfusion support.

• Prior allogeneic transplant (prior autologous stem cell transplant > 6 months prior to study entry is permitted)

• Prior exposure to a PI3K inhibitor (e.g., idelalisib/GS-1101, duvelisib) or a Bruton's tyrosine kinase (BTK) inhibitor

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