Phase 1/2a Study of BAL101553 as 48-hour Infusions in Patients With Advanced Solid Tumors or Recurrent Glioblastoma

NCT02895360 | Completed Phase 1 Results

• 1 other identifier: CDI-CS-003
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 6

Brief Summary

Single-agent, open-label, multi-center sequential dose escalation and expansion study of BAL101553, administered as an intravenous (IV) infusion over 48 hours to adults with advanced or recurrent solid tumors or recurrent glioblastoma.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of BAL101553

  First 28-day treatment cycle dose limiting toxicities (DLT) graded according to 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

  28 day cycle

Secondary Outcomes (6)

• Safety and Tolerability of BAL101553 Treatment Based on Number of Patients With Related Treatment-emergent Adverse Events (TEAEs) in the Phase 1 and Phase 2a Safety Population at Various Dose Levels and Indication

  TEAEs with onset on or after Day 1 of the study and until 28 days after the last dose

• AUC of BAL101553 and BAL27862

  0 to 168 hours post-dose at Day 1 of Cycle 1 and Cycle 2 in each cohort in Phase 1, 28-day cycles

• Cmax of BAL101553 and BAL27862

  Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2.

• Tmax of BAL101553 and BAL27862

  Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2.

• Bioavailability of Daily Oral BAL101553 Measured by BAL27862 in Phase 1

  Relative oral bioavailability, calculated as dose-normalized AUC0-τ following oral administration on Cycle 2 Day 21 divided by dose normalized AUC0-∞ following IV administration on Cycle 1 Day 1 for each cohort.

Study Arms (2)

Phase 1

EXPERIMENTAL

Fixed 3+3 dose escalation of BAL101553 in patients with advanced solid tumors

Drug: BAL101553

Phase 2a

EXPERIMENTAL

BAL101553 at MTD in patients with platinum-resistant/refractory ovarian cancer or recurrent glioblastoma

Drug: BAL101553 at MTD

Interventions

BAL101553 DRUG

BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; oral capsule daily for one week during Cycle 2 (study days 15-21)

Phase 1

BAL101553 at MTD DRUG

BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; treatment with maximum tolerated dose (MTD)

Phase 2a

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
• Phase 1: Patients with either histologically or cytologically confirmed advanced or recurrent solid tumor, who failed standard therapy or for whom no effective standard therapy is available.
• Phase 2a: Patients with platinum-resistant/refractory ovarian, fallopian tube or primary peritoneal cancer (high-grade serous, endometrioid, or carcinosarcoma histotypes) or glioblastoma in first relapse.
• Patients with solid tumors must have measurable disease according to Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1.
• Patients with recurrent glioblastoma must have measurable disease defined by contrast-enhancing magnetic resonance imaging.
• Life expectancy ≥ 12 weeks
• Acceptable organ and marrow function at baseline (protocol defined laboratory parameters)
• Patients with solid tumors must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 and patients with recurrent glioblastoma must have an ECOG performance status ≤ 2.

You may not qualify if:

• Patients with 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 glioblastoma 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, or have been treated previously with bevacizumab.
• Patients who have had prior exposure to BAL101553.
• Peripheral neuropathy ≥ CTCAE grade 2.
• Uncontrolled intercurrent illness that would unduly increase the risk of toxicity or limit compliance with study requirements
• Systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg at the screening visit.
• Blood pressure (BP) combination treatment with more than two antihypertensive medications.
• Women who are pregnant or breast-feeding. Men or women of reproductive potential who are not willing to apply effective birth control.

Sponsors & Collaborators

• Basilea Pharmaceutica: lead

Study Sites (6)

Oncology Institute of Southern Switzerland; Ospedale Regionale San Giovanni Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Cantonal Hospital of Grisons, Department of Oncology/ Haematology

Chur, 7000, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

Cantonal Hospital of St. Gallen, Dep. Medical Oncology & Hematology

Sankt Gallen, 9007, Switzerland

Location

UniversitaetsSpital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (2)

• Joerger M, Hundsberger T, Haefliger S, von Moos R, Hottinger AF, Kaindl T, Engelhardt M, Marszewska M, Lane H, Roth P, Stathis A. Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study. Invest New Drugs. 2023 Apr;41(2):267-275. doi: 10.1007/s10637-023-01336-9. Epub 2023 Feb 16.

  PMID: 36792805 DERIVED

• Joerger M, Stathis A, Metaxas Y, Hess D, Mantiero M, Mark M, Volden M, Kaindl T, Engelhardt M, Larger P, Lane H, Hafner P, Levy N, Stuedeli S, Sessa C, von Moos R. A Phase 1 study of BAL101553, a novel tumor checkpoint controller targeting microtubules, administered as 48-h infusion in adult patients with advanced solid tumors. Invest New Drugs. 2020 Aug;38(4):1067-1076. doi: 10.1007/s10637-019-00850-z. Epub 2019 Aug 30.

  PMID: 31471863 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

lisavanbulin

Results Point of Contact

• Title: Thomas Kaindl, MD, Global Medical Director, Oncology
• Organization: Basilea Pharmaceutica International Ltd.

Thomas.Kaindl@basilea.com

+41615671505

Study Officials

• Thomas Kaindl, MD

  Basilea Pharmaceutica

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 5, 2016
• First Posted: September 9, 2016
• Study Start: August 24, 2016
• Primary Completion: August 7, 2020
• Study Completion: August 7, 2020
• Last Updated: May 10, 2023
• Results First Posted: October 11, 2021

Record last verified: 2023-05

Locations

CH (6)