Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors or Glioblastoma or High-grade Glioma

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

First in human, open-label, sequential dose escalation and expansion study of oral BAL101553 in adult patients with advanced solid tumors and adult patients with recurrent or progressive glioblastoma or high-grade glioma.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Basilea Pharmaceutica

Criteria

Inclusion Criteria:

1. Age ≥ 18 years

2. Patients who have in the

Phase 1 portion either of the following:

1. a histologically- or cytologically confirmed advanced or recurrent solid tumor, who failed standard therapy, or for whom no effective standard therapy is available to them

2. histologically-confirmed GBM or high-grade glioma, with progressive or recurrent disease after prior radiotherapy, with or without chemotherapy. This will also include patients with histologically-confirmed low-grade glioma who present with unequivocal evidence by imaging of transformation to high-grade glioma/GBM.

Phase 2 portion: Recurrent, histologically confirmed, glioblastoma with tumor tissue positive for EB1; eligible are patients with de novo glioblastoma after prior radical chemo-radiotherapy or secondary glioblastoma after prior chemotherapy or radiotherapy.

3. Patients must have measurable disease.

4. Life expectancy ≥ 12 weeks

5. Acceptable organ and marrow function at baseline (protocol defined laboratory parameters)

6. Patients with advanced solid tumors must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 and patients with recurrent or progressive glioblastoma must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

7. Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

1. Patients with advanced or recurrent solid tumors who have received chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks prior to starting study drug or who have not recovered from side effects of prior therapies.

Patients with recurrent or progressive GBM or high-grade glioma who have: received radiotherapy within 12 weeks, unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field, or there is histological confirmation of unequivocal tumor progression; received administration of prior antitumor chemotherapy within 4 weeks, or within 6 weeks for nitrosoureas; undergone surgical resection within 4 weeks or a stereotactic biopsy/core biopsy within 1 week prior to starting study drug.

2. Patients who have had prior exposure to BAL1015533.

3. Inability to swallow oral medication

4. Increase in steroid dose in GBM or high-grade glioma patients within 5 days prior to first study-drug administration or requirement for > 6 mg/day dexamethasone or equivalent for symptom control.

5. Patients with gastrointestinal disease or those who have had a procedure that is expected to interfere with the oral absorption or tolerance of BAL101553

6. Symptomatic brain metastases or leptomeningeal disease, indicative of active disease, in patients with advanced or recurrent solid tumors.

7. Peripheral neuropathy ≥ CTCAE grade 2.

8. Uncontrolled intercurrent illness that would unduly increase the risk of toxicity or limit compliance with study requirements

9. Systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 100 mmHg at the screening visit.

10. Blood pressure (BP) combination treatment with more than two antihypertensive medications.

11. Women who are pregnant or breast-feeding. Men or women of reproductive potential who are not willing to apply effective birth control

12. Other protocol-defined exclusion criteria may apply.