Neoplasms
Conditions
Keywords
Advanced solid tumors, Recurrent glioblastoma, High-grade glioma
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).
Detailed description
This was the first study of the oral formulation (hard capsules) of lisavanbulin. Lisavanbulin was administered once daily during each day of a 28-day treatment cycle to adults with advanced or recurrent solid tumors or recurrent or progressive GBM / HGG who had failed standard therapy, or for whom no effective standard therapy was available. In Phase 1, the highest dose of lisavanbulin was determined that could safely be given to adults with advanced or recurrent solid tumors, recurrent or progressive GBM / HGG. In Phase 2a, the tolerability and potential anticancer activity of oral lisavanbulin was assessed in patients with recurrent GBM whose tumor tissue tests positive for end-binding protein 1 (EB1). The study also measured pharmacokinetics.
Interventions
DRUGLisavanbulin Phase 1 dose escalation portion
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
DRUGLisavanbulin Phase 2a expansion portion
Recommended Phase 2 dose (RP2D) of 25 mg/day lisavanbulin hard capsules containing 5 mg study drug was administered once daily.
Sponsors
Basilea Pharmaceutica
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Age ≥ 18 years 2. Patients who had 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 was available to them 2. 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. 3. 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. 4. Life expectancy ≥ 12 weeks 5. Acceptable organ and marrow function at baseline (protocol defined laboratory parameters) 6. 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 Main
Exclusion criteria
1. 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; 2. Patients who have had prior exposure to lisavanbulin 3. Inability to swallow oral medication 4. 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. 5. Patients with gastrointestinal disease or those who have had a procedure that was expected to interfere with the oral absorption or tolerance of lisavanbulin 6. Symptomatic brain metastases or leptomeningeal disease, which was indicative of active disease, in patients with advanced or recurrent solid tumors. 7. Peripheral neuropathy ≥ CTCAE grade 2. 8. Uncontrolled intercurrent illness that would have unduly increased 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 were pregnant or breast-feeding. Men or women of reproductive potential who were not willing to apply effective birth control
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Maximum Tolerated Dose (MTD) of Daily Oral Lisavanbulin | During first 28 day cycle | 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 |
| Phase 2a: Best Objective Response | Until the study discontinuation, on average 161 days (maximum of 381 days) | 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 |
| Phase 2a: Objective Response Rate (ORR) | Until the study discontinuation, on average 161 days (maximum of 381 days) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Pharmacokinetic parameter Area under the plasma concentration versus time curve AUC of avanbulin (BAL27862) Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862). |
| Phase 1: Best Objective Response | Until the end of treatment, on average 151 days (maximum of 1653 days), every other 28 day cycle | The best objective response was calculated as the proportion of patients responding (i.e., with a best observed objective response of complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 for patients with advanced or recurrent solid tumors); and based on RANO criteria for patients with recurrent or progressive GBM / HGG |
| Phase 1: Objective Response Rate (ORR) | Until the study discontinuation, on average 151 days (maximum 1653 days), every other 28 day cycle | The ORR was calculated as the percentage of patients (rate) with complete and partial responses and its 95% CI based on RECIST criteria v1.1 for patients with advanced or recurrent solid tumors; and based on RANO criteria for patients with recurrent or progressive GBM / HGG |
| 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) | Number of patients experiencing treatment-emergent adverse events (TEAE) of CTCAE Grade 3 or 4 |
| Phase 2a: PFS at 6 Months | 6 months | Percentage of patients without disease progression based on RANO criteria 6 months after the start of treatment. The values were determined using the Kaplan-Meier and Brookmeyer-Crowley methods. |
| Phase 2a: Overall Survival (OS) at 12 Months | 1 year | Percentage of patients alive 12 months after the start of treatment. The values were determined using the Kaplan-Meier and Brookmeyer-Crowley methods. |
| Phase 2a: PFS | 1 year | PFS was defined as the interval between the date of drug administration and the earliest date of objective disease progression based on RANO criteria for patients with recurrent or progressive GBM / HGG. Patients who have not progressed or died at the end of the study were censored at the time of their latest objective tumor assessment. |
| 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 | Pharmacokinetic parameter Peak Plasma Concentration Cmax of avanbulin Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862) |
| 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 | Pharmacokinetic parameter Time to Peak Plasma Concentration Tmax of avanbulin (BAL27862) Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862). |
Countries
Belgium, Germany, Switzerland, United Kingdom
Participant flow
Pre-assignment details
In the Phase 1 study, a total of 29 screening-failures occurred. Thus a total of 72 patients with advanced solid tumors, recurrent or progressive glioblastoma (GBM) or high-grade glioma (HGG) were enrolled in this Phase 1 and Phase 2a study.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 2 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 3 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 4 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 3 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 3 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 7 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 7 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 3 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 4 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 3 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 7 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 3 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 8 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily | 3 |
| Phase 2a Patients With Recurrent GBM: Lisavanbulin 25 mg/Day RP2D of 25 mg/day lisavanbulin hard capsules containing 5 mg study drug was administered once daily | 18 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 2 | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 2 | 2 |
| Overall Study | Patient enrolled in post-trial access | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 6 |
| Overall Study | Progressive disease | 3 | 3 | 3 | 4 | 4 | 1 | 4 | 3 | 6 | 2 | 7 | 1 | 10 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 2 mg/Day | Total | Phase 2a Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 4 mg/Day |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 21.94 | 55.7 years STANDARD_DEVIATION 12.52 | 55.6 years STANDARD_DEVIATION 10.43 | 51.3 years STANDARD_DEVIATION 16.74 | 53.6 years STANDARD_DEVIATION 9.78 | 45.3 years STANDARD_DEVIATION 11.5 | 42.3 years STANDARD_DEVIATION 9.62 | 53.7 years STANDARD_DEVIATION 7.77 | 53.8 years STANDARD_DEVIATION 9.95 | 65.7 years STANDARD_DEVIATION 12.06 | 64.4 years STANDARD_DEVIATION 7 | 61.0 years STANDARD_DEVIATION 16.55 | 63.3 years STANDARD_DEVIATION 6.51 | 66.7 years STANDARD_DEVIATION 10.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 69 Participants | 18 Participants | 2 Participants | 7 Participants | 3 Participants | 7 Participants | 3 Participants | 3 Participants | 3 Participants | 7 Participants | 7 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 31 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 6 Participants | 5 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 41 Participants | 15 Participants | 2 Participants | 6 Participants | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 7 | 0 / 7 | 0 / 3 | 0 / 4 | 0 / 3 | 1 / 7 | 0 / 3 | 1 / 8 | 0 / 3 | 7 / 18 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 7 | 7 / 7 | 3 / 3 | 4 / 4 | 3 / 3 | 5 / 7 | 3 / 3 | 7 / 8 | 3 / 3 | 18 / 18 |
| serious Total, serious adverse events | 0 / 3 | 2 / 3 | 0 / 3 | 4 / 7 | 5 / 7 | 1 / 3 | 0 / 4 | 0 / 3 | 2 / 7 | 1 / 3 | 4 / 8 | 2 / 3 | 8 / 18 |
Outcome results
Primary
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
Time frame: During first 28 day cycle
Population: MTD population: All patients from the safety set who met the following during the first 28-day treatment Cycle 1:~* Received at least one dose of lisavanbulin and had experienced a DLT~* Received at least 24 of the scheduled 28 doses for daily lisavanbulin administration, were not experiencing a DLT, had been observed for ≥ 28 days following the first dose, and had been evaluated for safety
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 1: Maximum Tolerated Dose (MTD) of Daily Oral Lisavanbulin | 16 mg |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 1: Maximum Tolerated Dose (MTD) of Daily Oral Lisavanbulin | 30 mg |
Primary
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
Time frame: Until the study discontinuation, on average 161 days (maximum of 381 days)
Population: The efficacy evaluable population (EEP) was the subset of the Full Analysis Population (FAP) who had at least one post baseline RANO assessment after having received at least 6 weeks of study treatment.~For the primary endpoint, best objective response / objective response rate, the analysis was based on patients with measurable disease at baseline.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 2a: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 2a: Best Objective Response | Partial response | 1 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 2a: Best Objective Response | Stable disease | 4 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 2a: Best Objective Response | Progressive disease | 4 Participants |
Primary
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
Time frame: Until the study discontinuation, on average 161 days (maximum of 381 days)
Population: Number of patients in EEP with measurable disease at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 2a: Objective Response Rate (ORR) | 11.1 Percentage of participants |
Secondary
AUC of Avanbulin (BAL27862)
Pharmacokinetic parameter Area under the plasma concentration versus time curve AUC of avanbulin (BAL27862) Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862).
Time frame: 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
Population: The PK analysis set includes all patients who received at least one partial or complete dose of study drug (for the Phase 1 on Day 1 of Cycles 1 and 2, and for the Phase 2a only on Day 1 of Cycle 1) and had at least one post-baseline PK assessment
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | AUC of Avanbulin (BAL27862) | 34.040 h*ng/mL | Geometric Coefficient of Variation 0.84 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | AUC of Avanbulin (BAL27862) | 74.020 h*ng/mL | Geometric Coefficient of Variation 0.83 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | AUC of Avanbulin (BAL27862) | 180.060 h*ng/mL | Geometric Coefficient of Variation 0.15 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | AUC of Avanbulin (BAL27862) | 356.490 h*ng/mL | Geometric Coefficient of Variation 0.16 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | AUC of Avanbulin (BAL27862) | 258.460 h*ng/mL | Geometric Coefficient of Variation 0.32 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | AUC of Avanbulin (BAL27862) | 439.660 h*ng/mL | Geometric Coefficient of Variation 0.62 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | AUC of Avanbulin (BAL27862) | 823.980 h*ng/mL | Geometric Coefficient of Variation 0.35 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | AUC of Avanbulin (BAL27862) | 896.420 h*ng/mL | Geometric Coefficient of Variation 0.54 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | AUC of Avanbulin (BAL27862) | 1014.130 h*ng/mL | Geometric Coefficient of Variation 0.65 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | AUC of Avanbulin (BAL27862) | 1265.130 h*ng/mL | Geometric Coefficient of Variation 0.41 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | AUC of Avanbulin (BAL27862) | 1649.350 h*ng/mL | Geometric Coefficient of Variation 0.25 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | AUC of Avanbulin (BAL27862) | 230.800 h*ng/mL | Geometric Coefficient of Variation 0.8 |
| Phase 2a Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | AUC of Avanbulin (BAL27862) | 331.800 h*ng/mL | Geometric Coefficient of Variation 1.76 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | AUC of Avanbulin (BAL27862) | 692.230 h*ng/mL | Geometric Coefficient of Variation 0.16 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | AUC of Avanbulin (BAL27862) | 814.930 h*ng/mL | Geometric Coefficient of Variation 0.46 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | AUC of Avanbulin (BAL27862) | 344.540 h*ng/mL | Geometric Coefficient of Variation 0.58 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | AUC of Avanbulin (BAL27862) | 507.360 h*ng/mL | Geometric Coefficient of Variation 0.74 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | AUC of Avanbulin (BAL27862) | 575.060 h*ng/mL | Geometric Coefficient of Variation 0.44 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | AUC of Avanbulin (BAL27862) | 790.340 h*ng/mL | Geometric Coefficient of Variation 0.11 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | AUC of Avanbulin (BAL27862) | 1055.130 h*ng/mL | Geometric Coefficient of Variation 0.25 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | AUC of Avanbulin (BAL27862) | 1296.470 h*ng/mL | Geometric Coefficient of Variation 0.37 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | AUC of Avanbulin (BAL27862) | 1264.610 h*ng/mL | Geometric Coefficient of Variation 0.32 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | AUC of Avanbulin (BAL27862) | 1146.110 h*ng/mL | — |
| Phase 2a Cycle 1, Day 1 Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | AUC of Avanbulin (BAL27862) | 713.710 h*ng/mL | Geometric Coefficient of Variation 0.48 |
Secondary
Cmax of Avanbulin (BAL27862)
Pharmacokinetic parameter Peak Plasma Concentration Cmax of avanbulin Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862)
Time frame: 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
Population: The PK analysis set includes all patients who received at least one partial or complete dose of study drug (for the Phase 1 on Day 1 of Cycles 1 and 2, and for the Phase 2a only on Day 1 of Cycle 1) and had at least one post-baseline PK assessment
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Cmax of Avanbulin (BAL27862) | 6.900 ng/mL | Geometric Coefficient of Variation 0.58 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Cmax of Avanbulin (BAL27862) | 9.800 ng/mL | Geometric Coefficient of Variation 0.49 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Cmax of Avanbulin (BAL27862) | 23.400 ng/mL | Geometric Coefficient of Variation 0.44 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Cmax of Avanbulin (BAL27862) | 40.880 ng/mL | Geometric Coefficient of Variation 0.27 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Cmax of Avanbulin (BAL27862) | 29.190 ng/mL | Geometric Coefficient of Variation 0.49 |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Cmax of Avanbulin (BAL27862) | 44.270 ng/mL | Geometric Coefficient of Variation 0.64 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Cmax of Avanbulin (BAL27862) | 120.260 ng/mL | Geometric Coefficient of Variation 0.49 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Cmax of Avanbulin (BAL27862) | 109.560 ng/mL | Geometric Coefficient of Variation 0.49 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Cmax of Avanbulin (BAL27862) | 116.630 ng/mL | Geometric Coefficient of Variation 0.58 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Cmax of Avanbulin (BAL27862) | 147.730 ng/mL | Geometric Coefficient of Variation 0.41 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Cmax of Avanbulin (BAL27862) | 159.020 ng/mL | Geometric Coefficient of Variation 0.08 |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Cmax of Avanbulin (BAL27862) | 35.260 ng/mL | Geometric Coefficient of Variation 0.56 |
| Phase 2a Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | Cmax of Avanbulin (BAL27862) | 48.930 ng/mL | Geometric Coefficient of Variation 0.91 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Cmax of Avanbulin (BAL27862) | 75.130 ng/mL | Geometric Coefficient of Variation 0.11 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Cmax of Avanbulin (BAL27862) | 114.890 ng/mL | Geometric Coefficient of Variation 0.43 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Cmax of Avanbulin (BAL27862) | 64.110 ng/mL | Geometric Coefficient of Variation 0.46 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Cmax of Avanbulin (BAL27862) | 78.700 ng/mL | Geometric Coefficient of Variation 0.64 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Cmax of Avanbulin (BAL27862) | 103.950 ng/mL | Geometric Coefficient of Variation 0.47 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Cmax of Avanbulin (BAL27862) | 95.370 ng/mL | Geometric Coefficient of Variation 0.11 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Cmax of Avanbulin (BAL27862) | 146.500 ng/mL | Geometric Coefficient of Variation 0.58 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Cmax of Avanbulin (BAL27862) | 146.010 ng/mL | Geometric Coefficient of Variation 0.34 |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Cmax of Avanbulin (BAL27862) | 159.100 ng/mL | Geometric Coefficient of Variation 0.65 |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Cmax of Avanbulin (BAL27862) | 190.000 ng/mL | — |
| Phase 2a Cycle 1, Day 1 Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | Cmax of Avanbulin (BAL27862) | 98.210 ng/mL | Geometric Coefficient of Variation 0.41 |
Secondary
Number of Patients With CTCAE Grade 3-4 TEAEs
Number of patients experiencing treatment-emergent adverse events (TEAE) of CTCAE Grade 3 or 4
Time frame: 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)
Population: Safety population: All patients who received at least one full or partial dose of lisavanbulin and had at least one post-baseline safety assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 3 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 2 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 1 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 1 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 2 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 3 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 2 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 2 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 4 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 1 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 2 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 1 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 2 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 3 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 3 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 6 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 2 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 4 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 4 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 2 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 1 Participants |
| Phase 2a Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients without TEAEs of Grade 3-4 | 10 Participants |
| Phase 2a Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with related TEAEs of Grade 3-4 | 3 Participants |
| Phase 2a Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | Number of Patients With CTCAE Grade 3-4 TEAEs | Number of patients with only unrelated TEAEs of Grade 3-4 | 5 Participants |
Secondary
Phase 1: 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 response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 for patients with advanced or recurrent solid tumors); and based on RANO criteria for patients with recurrent or progressive GBM / HGG
Time frame: Until the end of treatment, on average 151 days (maximum of 1653 days), every other 28 day cycle
Population: Full analysis population (FAP): All patients who received at least one partial or complete dose of study drug, based on the intent-to-treat (ITT) principle
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 1: Best Objective Response | Progressive disease | 2 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 1: Best Objective Response | Stable disease | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 1: Best Objective Response | Stable disease | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 1: Best Objective Response | Progressive disease | 3 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Progressive disease | 2 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Stable disease | 1 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Phase 1: Best Objective Response | Stable disease | 4 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Phase 1: Best Objective Response | Missing | 1 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Phase 1: Best Objective Response | Progressive disease | 2 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Progressive disease | 4 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Stable disease | 3 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Stable disease | 1 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Progressive disease | 2 Participants |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Progressive disease | 4 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Stable disease | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Phase 1: Best Objective Response | Stable disease | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Phase 1: Best Objective Response | Progressive disease | 2 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Progressive disease | 5 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Phase 1: Best Objective Response | Stable disease | 2 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Phase 1: Best Objective Response | Progressive disease | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Phase 1: Best Objective Response | Partial response | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Phase 1: Best Objective Response | Stable disease | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Stable disease | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Complete response | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Missing | 1 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Phase 1: Best Objective Response | Progressive disease | 5 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Phase 1: Best Objective Response | Partial response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Phase 1: Best Objective Response | Complete response | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Phase 1: Best Objective Response | Missing | 0 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Phase 1: Best Objective Response | Stable disease | 2 Participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Phase 1: Best Objective Response | Progressive disease | 1 Participants |
Secondary
Phase 1: Objective Response Rate (ORR)
The ORR was calculated as the percentage of patients (rate) with complete and partial responses and its 95% CI based on RECIST criteria v1.1 for patients with advanced or recurrent solid tumors; and based on RANO criteria for patients with recurrent or progressive GBM / HGG
Time frame: Until the study discontinuation, on average 151 days (maximum 1653 days), every other 28 day cycle
Population: FAP (Phase 1 portion of the study)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Phase 1: Objective Response Rate (ORR) | 33.3 Percentage of patients |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Phase 1: Objective Response Rate (ORR) | 12.5 Percentage of patients |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Phase 1: Objective Response Rate (ORR) | 0 Percentage of patients |
Secondary
Phase 2a: Overall Survival (OS) at 12 Months
Percentage of patients alive 12 months after the start of treatment. The values were determined using the Kaplan-Meier and Brookmeyer-Crowley methods.
Time frame: 1 year
Population: FAP and EEP
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 2a: Overall Survival (OS) at 12 Months | 42.9 percentage of patients |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 2a: Overall Survival (OS) at 12 Months | 55.6 percentage of patients |
Secondary
Phase 2a: PFS
PFS was defined as the interval between the date of drug administration and the earliest date of objective disease progression based on RANO criteria for patients with recurrent or progressive GBM / HGG. Patients who have not progressed or died at the end of the study were censored at the time of their latest objective tumor assessment.
Time frame: 1 year
Population: PFS was summarized for the FAP and EEP
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 2a: PFS | 2.5 Months |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 2a: PFS | 3.5 Months |
Secondary
Phase 2a: PFS at 6 Months
Percentage of patients without disease progression based on RANO criteria 6 months after the start of treatment. The values were determined using the Kaplan-Meier and Brookmeyer-Crowley methods.
Time frame: 6 months
Population: FAP and EEP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Phase 2a: PFS at 6 Months | 31.3 Percentage of participants |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Phase 2a: PFS at 6 Months | 43.3 Percentage of participants |
Secondary
Tmax of Avanbulin (BAL27862)
Pharmacokinetic parameter Time to Peak Plasma Concentration Tmax of avanbulin (BAL27862) Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862).
Time frame: 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
Population: The PK analysis set includes all patients who received at least one partial or complete dose of study drug (for the Phase 1 on Day 1 of Cycles 1 and 2, and for the Phase 2a only on Day 1 of Cycle 1) and had at least one post-baseline PK assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin | Tmax of Avanbulin (BAL27862) | 2.0 Hours |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin | Tmax of Avanbulin (BAL27862) | 1.2 Hours |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 8 mg/Day | Tmax of Avanbulin (BAL27862) | 1.1 Hours |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 16 mg/Day | Tmax of Avanbulin (BAL27862) | 1.1 Hours |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 20 mg/Day | Tmax of Avanbulin (BAL27862) | 3.0 Hours |
| Phase 1 Patients With Advanced or Recurrent Solid Tumors: Lisavanbulin 30 mg/Day | Tmax of Avanbulin (BAL27862) | 2.0 Hours |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 8 mg/Day | Tmax of Avanbulin (BAL27862) | 1.1 Hours |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Tmax of Avanbulin (BAL27862) | 1.2 Hours |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Tmax of Avanbulin (BAL27862) | 1.0 Hours |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Tmax of Avanbulin (BAL27862) | 1.1 Hours |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Tmax of Avanbulin (BAL27862) | 2.0 Hours |
| Phase 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Tmax of Avanbulin (BAL27862) | 1.5 Hours |
| Phase 2a Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | Tmax of Avanbulin (BAL27862) | 1.0 Hours |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Tmax of Avanbulin (BAL27862) | 1.1 Hours |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 15 mg/Day | Tmax of Avanbulin (BAL27862) | 1.1 Hours |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Tmax of Avanbulin (BAL27862) | 1.2 Hours |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 20 mg/Day | Tmax of Avanbulin (BAL27862) | 1.1 Hours |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Tmax of Avanbulin (BAL27862) | 1.0 Hours |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 25 mg/Day | Tmax of Avanbulin (BAL27862) | 2.0 Hours |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Tmax of Avanbulin (BAL27862) | 2.0 Hours |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 30 mg/Day | Tmax of Avanbulin (BAL27862) | 2.0 Hours |
| Phase 1 Cycle 1, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Tmax of Avanbulin (BAL27862) | 2.2 Hours |
| Phase 1 Cycle 2, Day 1 Patients With Recurrent or Progressive GBM / HGG: Lisavanbulin 35 mg/Day | Tmax of Avanbulin (BAL27862) | 1.0 Hours |
| Phase 2a Cycle 1, Day 1 Patients With Recurrent GBM: Lisavanbulin 25 mg/Day | Tmax of Avanbulin (BAL27862) | 2.0 Hours |