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

NCT05053880 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: ACT001-US-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Recurrent Glioblastoma Multiforme(GBM)

Keywords

GBM; Brain; Blastoma; Neoplasm

Outcome Measures

Primary Outcomes (9)

• 1b-Incidence, type and severity of treatment-emergent AEs (TEAEs)

  Approximately 7 months. Each cycle is 21 days; from start of first dose with investigational product until completion of the last study related procedure (including follow-up for safety assessments- 30days after last dose)

• 1b-Dose limiting toxicities (DLTs)

  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

  From first dose of study therapy until the end of the first post-surgery cycle (Cycle 1, Day 21).

• 1b-Mean changes in vital sign measurements-Heart Rate

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

  Approximately 8months/ patient. Each cycle is 21 days. Start at screening, Pre-surgical Treatment Period, Cycle 1 and each subsequent Cycle and 30 days after last dose

• 1b-Mean changes in vital sign measurements- supine blood pressure

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

  Approximately 8months/ patient.Each cycle is 21 days. Start at screening, Pre-surgical Treatment Period, Cycle 1 and each subsequent Cycle and 30 days after last dose

• 1b-Mean changes in vital sign measurements- body temperature

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

  Approximately 8months/ patient. Each cycle is 21 days. Start at screening, Pre-surgical Treatment Period, Cycle 1 and each subsequent Cycle and 30 days after last dose

• 1b-Mean changes in vital sign measurements- respiratory rate

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

  Approximately 8months/ patient. Each cycle is 21 days. Start at screening, Pre-surgical Treatment Period, Cycle 1 and each subsequent Cycle and 30 days after last dose

• 1b-Mean changes in electrocardiogram (ECG) parameters

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

  approximately 8months/patient. Each cycle is 21 days. Start at screening, Pre-surgical Treatment Period, Cycle 1 and each subsequent Cycle and 30 days after last dose

• 1b-Mean changes in Karnofsky Performance Scale score

  Mean change from baseline in Karnofsky Performance Scale score

  Approximately 8 months/patient. Each cycle is 21 days. Start at screening, Pre-surgical Treatment Period, Cycle 1 and each subsequent Cycle and 30 days after last dose

• 2a-Progression free survival (PFS) at 6 months

  Six months after initiation of study therapy

Secondary Outcomes (5)

• 1b-Incidence of DLTs according to the MTD/RP2D evaluation process.

  From first dose of study therapy (per surgery) until the end of the first post-surgery cycle (Cycle 1, Day 21). Each cycle is 21 days.

• 1b- Pharmacokinetics (PK) of ACT001 in Plasma concentrations in tumor.

  PK analysis will be collected on Day 1 of the pre surgical treatment period.

• 2a-Overall survival

  Approximately 7months/patient- screening period is not included. Cycle 1 Day 1 until death, loss to follow-up, withdrawal of consent, date of disease progression or whichever occurs first

• 2a-Incidence, type and severity of TEAEs

  From start of dosing until 30 days after the last dose of ACT001

• 2a-Concentration of ACT001 in resected tumor biopsy tissue.

  Tissue at Surgical Resection only.

Study Arms (2)

1b dose exploration

EXPERIMENTAL

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.

Drug: ACT001

2a- Randomized/Two-treatment Arm

EXPERIMENTAL

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).

Drug: ACT001 + Pembrolizumab

Interventions

ACT001 DRUG

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.

1b dose exploration

ACT001 + Pembrolizumab DRUG

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.

2a- Randomized/Two-treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has provided written informed consent.
• ≥ 18 years old at time of screening visit.
• Histologically confirmed GBM at the time of diagnosis.
• First or second relapse by the time of consenting.
• Tumor progression (magnetic resonance imaging \[MRI\], defined by RANO) post prior treatments.
• Feasibility for re-surgery.
• Karnofsky Performance Status ≥ 70% (requires occasional assistance, but able to care for most of their needs, equivalent to \< ECOG 2).
• Must be ≥ 4 weeks from administration of last dose of cancer therapy (including radiation therapy or chemotherapy). The patient must have recovered from all treatment-related toxicities to less than grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
• Life expectancy of ≥ 3 months.
• Adequate organ function (absolute neutrophil count ≥1.5 x 109 /L, lymphocytes ≥ 0.5 x 109 /L, platelets ≥ 75 x 109 /L, hemoglobin ≥ 10 g/dl; total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5.0 x ULN if liver metastasis); plasma creatinine ≤ 1.5 x ULN; QTc \< 450 ms (male), \< 470 ms (female).
• Female patients are eligible if they are of:
• Non-childbearing potential, defined as
• Previous hysterectomy or bilateral oophorectomy
• Previous bilateral tubal ligation
• Post-menopausal (total cessation of menses for ≥ 1 year)

You may not qualify if:

• The patient has uncontrolled infection.
• The patient has serious diseases such as unstable angina pectoris, myocardial infarction in the past 6 months, heart failure (New York Heart Association class \> II) or stroke within 6 months prior to the enrollment.
• A gastrointestinal absorption disorder that would limit the bioavailability of oral drugs or if patient cannot take oral drugs.
• Uncontrolled brain metastases or spinal cord compression. Patients who were treated with surgical resection or radiation therapy completing at least 4 weeks earlier are eligible if they are neurologically stable, not taking glucocorticoids and have a follow-up. MRI scan performed within the previous 4 weeks showing no tumor progression.
• Pre-existing allergy to ACT001 or related compounds.
• A patient has active autoimmune disease managed by systemic treatments in the past 2 years (i.e. the use of corticosteroids, immunosuppressive drugs or other disease modifying agents). Of note, a replacement therapy, e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic treatment.
• A known history of, or any evidence of an active non-infectious pneumonitis.
• Treatment with cancer therapies such as chemotherapy or radiation therapy either currently or within 4 weeks of ACT001 dosing. An exception is focal radiation for symptomatic bone metastases, which must not be within 2 weeks of ACT001 dosing.
• History of treatment with immune CPB and Avastin (or other antiangiogenic or anti-vascular endothelial growth factor agents).
• High dose of corticosteroids (\> 4mg/day of dexamethasone or equivalent for at least 3 consecutive days) within two weeks of enrolment for GBM treatment.
• A patient has received other systemic immunosuppressive treatments such as mTOR inhibitor everolimus four weeks prior to registration.
• A patient has a diagnosis of ongoing immunodeficiency due to other diseases such as human immunodeficiency virus (HIV) infection.
• Unresolved toxicity from prior antitumor therapy, defined as toxicities (excluding alopecia) that have not resolved to \< Grade 2 as scored using the CTCAE current version. Exceptions may be allowed for stable toxicities after discussion with the investigator and sponsor.
• Major surgery within 30 days of commencing first study therapy.
• Pregnant or breast-feeding females.

Sponsors & Collaborators

• Accendatech USA Inc.: lead
• C3 Research Associates: collaborator
• Avance Clinical Pty Ltd.: collaborator

Study Sites (1)

UT MD Anderson Cancer Center, Dept of Neuro-Oncology

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Neoplasms

Interventions

ACT001; pembrolizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Doug Cai, MD

  Accendatech USA Inc.

  STUDY DIRECTOR

Central Study Contacts

C3 Research Associates

CONTACT

+1 206 686 4644; ACT001-US-001@c3-research.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: September 23, 2021
• Study Start: September 22, 2021
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2023
• Last Updated: November 19, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)