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Glioblastoma

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Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

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Neoplasms, Glandular and Epithelial

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All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

1b dose exploration for 18 patients - The starting dose of ACT001 will be administered in combination with a single intravenous (IV) infusion of Pembrolizumab. After recovery from surgical resection, dosing will resume on a 3 weekly cycle and will consist of Pembrolizumab (standard dosing) and daily ACT001. Evaluation of a dose level of at least three (3) patients after completing one cycle of treatment post-surgery is required prior to commencing the next dose level.

30 Patients will be randomized to Arm A or Arm B at a ratio of 1 (Arm A) : 2 (Arm B). 10 patients will be randomized to the Pembrolizumab only arm (Arm A) and 20 patients will be randomized to the ACT001 plus Pembrolizumab arm (Arm B).

Phase1b - Starting approximately 2 weeks prior to the scheduled surgery, patient will receive an assigned dose of ACT001 by mouth in combination with a single dose of 200 mg pembrolizumab via an intravenous (IV-through a tube in vain) infusion in the clinic. Then patient will self administer ACT001 capsules twice daily by mouth, at the dose to which patient is assigned, until the evening prior to scheduled surgery. Patient will then undergo surgery to remove all or part of tumor. This a standard 3+3 dose escalation.

ACT001

Phase 2a - Starting approximately 2 weeks prior to the scheduled surgery, patient will receive a single dose of 200 mg pembrolizumab via an intravenous (IV) infusion in the clinic (an IV infusion means the drug will be delivered through a tube in your vein). Patient will then self-administer ACT001 capsules twice daily by mouth, at the dose to which patient is assigned, until the evening prior to scheduled surgery. Patient then will undergo surgery to remove all or part of tumor.

ACT001 + Pembrolizumab

C3 Research Associates

Shiao-Pei Weathers, MD

Vanessa Santiago, Sr Research Nurse

Doug Cai, MD

The current design provides a window to analyze the impact of the ACT001+Pembrolizumab combination on the tumor microenvironment and disease outcomes.

Phase 1b: The identified RP2D of combined ACT001 with Pembrolizumab will be determined by standard 3+3 dose escalation methodology among three ACT001 dosages (200mg, 400mg and 800mg, BID) with standard Pembrolizumab dosage. Patients will be dosed approximately 2 weeks prior to surgical resection with a single dose of Pembrolizumab and ACT001. Tumor resection will be performed and a biopsy will be obtained from the resected tumor tissue to evaluate the impact of the study drugs on the TME. After recovery from surgery, patients will resume ACT001 and Pembrolizumab until tumor progression (assessed by iRANO) or an AE requiring discontinuation of study drug. The Safety Monitoring Committee (SMC) will review the data available from all evaluable patients at each dose level prior to recommending escalation to the next dose level.

Phase 2a: Using the same dosing schedule and ACT001 dosage as determined in Phase 1b. Patients will be randomized to receive either Pembrolizumab only treatment (Arm A, 10 patients) or ACT001 plus Pembrolizumab treatment (Arm B, 20 patients).

Phase 1b dose exploration will enroll up to a maximum of 18 patients. Phase 2a, randomized/2-treatment arm part, will enroll up to 30 patients in two treatment arms. Arm A (treatment with Pembrolizumab) will enroll 10 patients. Arm B (treatment with the combination ACT001 plus Pembrolizumab) will enroll 20 patients.

A Study to Evaluate Safety and Efficacy of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme

A Phase 1b/2a Study of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme

A DLT is defined as any of the following

* Haematological toxicity

  * Grade 4 neutropenia
  * Grade ≥ 3 febrile neutropenia or neutropenic infection
  * Grade 4 thrombocytopenia
  * Grade 3 thrombocytopenia with clinically significant bleeding
* Non-haematological toxicity

  * Grade ≥ 3 nausea, vomiting or diarrhoea despite optimal supportive therapy
  * Grade ≥ 3 hypertension despite appropriate intervention
  * Other grade ≥ 3 non-haematological toxicity, except grade 3 fatigue or transient events (such as allergic reactions or electrolyte disturbances) that are readily controlled with medical therapy and/or are of no clinical concern

Mean change from baseline in vital sign measurements reported in beats/min (inclusive) at each study timepoint.

Mean change from baseline in vital sign measurements reported in mmHg at each study timepoint

Mean change from baseline in vital sign measurements reported in degrees Celsius (0C) at each study timepoint.

Mean change from baseline in vital sign measurements reported in bpm at each study timepoint

Mean change from baseline in electrocardiogram (ECG) parameters of heart rate, ventricular rate, PR interval, QRS duration, and QTcF.

Mean change from baseline in Karnofsky Performance Scale score

Determine ACT001 trough levels in tumor samples.

Overall survival (OS) is defined as time from start of ACT001 dosing at day 1 of cycle 1 until the date of death or date from any cause, assessed up to disease progression.

Summary of the treatment-emergent Adverse events experienced during treatment. Adverse events are assessed with Common Terminology Criteria for Adverse Events (CTCAE) 5.0. TEAEs are defined as any medical occurrence reported or observed after the start of dosing with investigational product until completion of the last study related procedure (including follow-up for safety assessments)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate Safety and Efficacy of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme	NCT05053880	Recurrent Gliob...	ACT001 ACT001 + Pembro...	18 Years -	Accendatech USA Inc.
A Study to Evaluate Safety and Efficacy of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme	NCT05053880	Recurrent Gliob...	ACT001 ACT001 + Pembro...	18 Years -	Accendatech USA Inc.
A Study to Evaluate Safety and Efficacy of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme	NCT05053880	Recurrent Gliob...	ACT001 ACT001 + Pembro...	18 Years -	Accendatech USA Inc.

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