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

NCT02490800 | Completed Phase 1 Results

• 1 other identifier: CDI-CS-002
• Study Type: interventional
• Target: 72
• Locations: 4 countries
• Sites: 13

Brief Summary

First in human, open-label, dose escalation (Phase I) and expansion study (Phase 2a) of oral lisavanbulin (BAL101553) in adult patients with advanced solid tumors and adult patients with recurrent or progressive glioblastoma (GBM) or high-grade glioma (HGG).

Conditions

Neoplasms

Keywords

Advanced solid tumors; Recurrent glioblastoma; High-grade glioma

Outcome Measures

Primary Outcomes (3)

• Phase 1: Maximum Tolerated Dose (MTD) of Daily Oral Lisavanbulin

  First 28-day treatment cycle dose limiting toxicities (DLT) graded according to Common Terminology Criteria for Adverse Events (CTCAE) in the MTD-determining population in Phase 1 based on the number of participants with adverse effects as measure of tolerability at various dose levels

  During first 28 day cycle

• Phase 2a: Best Objective Response

  The best objective response was calculated as the proportion of patients responding (i.e., with a best observed objective response of complete or partial response) based on "radiological assessment in neuro-oncology (RANO)" criteria

  Until the study discontinuation, on average 161 days (maximum of 381 days)

• Phase 2a: Objective Response Rate (ORR)

  The ORR was calculated as the percentage of patients (rate) with complete and partial responses and its 95% Confidence Interval (CI) based on RANO criteria

  Until the study discontinuation, on average 161 days (maximum of 381 days)

Secondary Outcomes (9)

• Number of Patients With CTCAE Grade 3-4 TEAEs

  TEAEs were defined as all events occurring after lisavanbulin treatment began and up to 28 days after last study drug administration which corresponded to a maximum of 1653 days (4,5 years)

• Cmax of Avanbulin (BAL27862)

  Plasma PK profiles were obtained on Cycle 1, Day 1 and on Cycle 2, Day 1 (pre-dose and from 0 up to 24 h post-dose) for all patients in the Phase 1 study who received lisavanbulin. For Phase 2 a study, PK parameters were obtained only on Cycle 1, Day 1

• Tmax of Avanbulin (BAL27862)

  Plasma PK profiles were obtained on Cycle 1, Day 1 and on Cycle 2, Day 1 (pre-dose and from 0 up to 24 h post-dose) for all patients in the Phase 1 study who received lisavanbulin. For Phase 2 a study, PK parameters were obtained only on Cycle 1, Day 1

• AUC of Avanbulin (BAL27862)

  Plasma PK profiles were obtained on Cycle 1, Day 1 and on Cycle 2, Day 1 (pre-dose and from 0 up to 24 h post-dose) for all patients in the Phase 1 study who received lisavanbulin. For Phase 2 a study, PK parameters were obtained only on Cycle 1, Day 1

• Phase 1: Best Objective Response

  Until the end of treatment, on average 151 days (maximum of 1653 days), every other 28 day cycle

Study Arms (2)

Phase 1 dose escalation portion

EXPERIMENTAL

Phase 1 dose escalation portion - an accelerated 3+3 titration design in patients with: 1. advanced or recurrent solid tumors 2. recurrent or progressive GBM / HGG

Drug: Lisavanbulin Phase 1 dose escalation portion

Phase 2a dose expansion portion

EXPERIMENTAL

Phase 2a expansion portion (Simon's two-stage design) - Patients with recurrent and EB1-positive GBM

Drug: Lisavanbulin Phase 2a expansion portion

Interventions

Lisavanbulin Phase 1 dose escalation portion DRUG

Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily in the dose range of 2 to 35 mg/day

Also known as: BAL101553

Phase 1 dose escalation portion

Lisavanbulin Phase 2a expansion portion DRUG

Recommended Phase 2 dose (RP2D) of 25 mg/day lisavanbulin hard capsules containing 5 mg study drug was administered once daily.

Also known as: BAL101553

Phase 2a dose expansion portion

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Patients who had in the Phase 1 portion either of the following:
• a histologically- or cytologically confirmed advanced or recurrent solid tumor, who failed standard therapy, or for whom no effective standard therapy was available to them
• histologically-confirmed GBM or HGG, with progressive or recurrent disease after prior radiotherapy, with or without chemotherapy. This also included patients with histologically-confirmed low-grade glioma who presented with unequivocal evidence by imaging of transformation to GBM / HGG
• Phase 2a dose expansion portion:
• Recurrent, histologically confirmed, glioblastoma with tumor tissue positive for EB1; eligible patients with de novo glioblastoma after prior radical chemo-radiotherapy or secondary glioblastoma after prior chemotherapy or radiotherapy.
• Phase 1: Patients had to have measurable disease; according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 for patients with advanced or recurrent solid tumors, and per radiological assessment in neuro-oncology (RANO) criteria for patients with recurrent or progressive GBM /HGG. Phase 2a: Patients had to be evaluable per RANO criteria.
• Life expectancy ≥ 12 weeks
• Acceptable organ and marrow function at baseline (protocol defined laboratory parameters)
• Patients with advanced solid tumors had to have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 and patients with recurrent or progressive glioblastoma had to have an ECOG performance status ≤ 2

You may not qualify if:

• Patients with advanced or recurrent solid tumors who had received chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks (2 weeks for single fraction of palliative radiotherapy, 6 weeks for nitrosoureas or mitomycin C) prior to starting study drug or who had not recovered from side effects of prior therapies
• Patients with recurrent or progressive GBM / HGG who had: received radiotherapy within 6 weeks (Phase 1) or 12 weeks (Phase 2a), unless there was a new area of enhancement consistent with recurrent tumor outside the radiation field; received administration of prior anti-tumor chemotherapy within 4 weeks, or within 6 weeks for nitrosoureas; undergone surgical resection within 4 weeks (Phase 2a: 2 weeks) or a stereotactic biopsy/core biopsy within 1 week prior to starting study drug;
• Patients who have had prior exposure to lisavanbulin
• Inability to swallow oral medication
• Increase in steroid dose in GBM or HGG patients within 5 days prior to first study-drug administration or requirement for \> 6 mg/day dexamethasone or equivalent for symptom control.
• Patients with gastrointestinal disease or those who have had a procedure that was expected to interfere with the oral absorption or tolerance of lisavanbulin
• Symptomatic brain metastases or leptomeningeal disease, which was indicative of active disease, in patients with advanced or recurrent solid tumors.
• Peripheral neuropathy ≥ CTCAE grade 2.
• Uncontrolled intercurrent illness that would have unduly increased the risk of toxicity or limit compliance with study requirements
• Systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 100 mmHg at the screening visit.
• Blood pressure (BP) combination treatment with more than two antihypertensive medications.
• Women who were pregnant or breast-feeding. Men or women of reproductive potential who were not willing to apply effective birth control

Sponsors & Collaborators

• Basilea Pharmaceutica: lead

Study Sites (13)

UZ Leuven

Leuven, 3000, Belgium

Location

Klinikum der Goethe-Universität Frankfurt

Frankfurt, 60528, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

Inselspital Universitätsspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

University College London NHS Foundation Trust

London, NW1 2BU, United Kingdom

Location

Sir Bobby Robson Cancer Trials Research Centre; Northern Centre for Cancer Care

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Lopez JS, Haefliger S, Plummer R, Clement PM, Jeffry Evans TR, Laubli H, Roth P, Kristeleit R, Brazil L, Tabatabai G, Wick A, Wunderlich B, Beebe K, Eisner JR, Lane H, Engelhardt M, Kaindl T, Hau P, Hundsberger T, Steinbach J. A phase 1/2a dose-finding study and biomarker assessment of oral lisavanbulin in patients with high-grade glioma or glioblastoma. Cell Rep Med. 2025 Jun 17;6(6):102165. doi: 10.1016/j.xcrm.2025.102165.

  PMID: 40532659 DERIVED

MeSH Terms

Conditions

Neoplasms; Glioblastoma; Glioma

Interventions

lisavanbulin

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Thomas Kaindl, MD
• Organization: Basilea Pharmaceutica International Ltd, Allschwil

thomas.kaindl@basilea.com

+41 61 567 15 24

Study Officials

• Thomas Kaindl, MD

  Basilea Pharmaceutica International Ltd, Allschwil

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 25, 2015
• First Posted: July 7, 2015
• Study Start: May 20, 2015
• Primary Completion: September 30, 2022
• Study Completion: November 24, 2022
• Last Updated: June 26, 2024
• Results First Posted: June 26, 2024

Record last verified: 2024-06

Locations

DE (4); GB (4); CH (4); BE (1)