Trial Outcomes & Findings for A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma (NCT NCT02315534)

NCT ID: NCT02315534

Last Updated: 2023-11-15

Results Overview

Number of patients who experienced a dose limiting toxicity following a dosing of BBI608

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 34 participants
• Primary outcome timeframe: 28 days after first administration of combination treatment (BBI608+TMZ)
• Results posted on: 2023-11-15

Participant Flow

There are no pre-assignment details, study arm was determined at patient enrollment to the study

Participant milestones

Measure	Candidates Whom Surgery is Recommended. BBI608 will be administered at the recommended phase 2 dose (RP2D) twice daily for 7(±2) days prior to planned surgical resection or biopsy of recurrent GBM. Upon the clinical recovery of the patient and at a time between 15-28 days after surgery, BBI608 will be administered orally, daily, each day of a 28 day cycle in combination with temozolomide	Candidates Whom Surgery is Not Recommended. Patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, each day of a 28 day cycle at the recommended phase 2 dose (RP2D) in combination with temozolomide
Overall Study STARTED	4	30
Overall Study Assessment of Dose-limiting Toxicity (DLT)	0	0
Overall Study Off Treatment Due to Radiologic Disease Progression (PD)	2	20
Overall Study Off Treatment Due to Clinically Unacceptable Toxicities	1	7
Overall Study Off Treatment Due to Patient Request	1	2
Overall Study Off Treatment Due to Clinical PD	0	1
Overall Study COMPLETED	4	30
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma

Baseline characteristics by cohort

Measure	Candidates Whom Surgery is Recommended. n=4 Participants Candidates who were candidates for repeat surgical resection	Candidates Whom Surgery is Not Recommended n=30 Participants Candidates who were not candidates for repeat surgical resection	Total n=34 Participants Total of all reporting groups
Age, Continuous	58.8 years STANDARD_DEVIATION 10.14 • n=5 Participants	54.6 years STANDARD_DEVIATION 15.54 • n=7 Participants	55.1 years STANDARD_DEVIATION 14.95 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	18 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	26 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Smoking Lifetime nonsmoker	3 Participants n=5 Participants	21 Participants n=7 Participants	24 Participants n=5 Participants
Smoking Current smoker	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Smoking Former smoker	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Weight	100.55 kilograms STANDARD_DEVIATION 26.345 • n=5 Participants	78.21 kilograms STANDARD_DEVIATION 16.170 • n=7 Participants	80.84 kilograms STANDARD_DEVIATION 13.608 • n=5 Participants
Height	177.25 centimeters STANDARD_DEVIATION 7.411 • n=5 Participants	173.91 centimeters STANDARD_DEVIATION 9.896 • n=7 Participants	174.30 centimeters STANDARD_DEVIATION 9.605 • n=5 Participants

PRIMARY outcome

Timeframe: 28 days after first administration of combination treatment (BBI608+TMZ)

Population: Up to the first 6 patients whom surgery was and wasn't recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be≥ 80% compliant to assigned dose to qualify for DLT analysis.

Number of patients who experienced a dose limiting toxicity following a dosing of BBI608

Outcome measures

Measure	Candidates Whom Surgery is Recommended. n=4 Participants The first 6 patients whom surgery was recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.	Candidates Whom Surgery is Not Recommended n=6 Participants The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.
Dose-limiting Toxicities (DLTs)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, assessed up to 6 months

Population: Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 6 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-6 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 6 months after treatment.

Outcome measures

Measure	Candidates Whom Surgery is Recommended. n=30 Participants The first 6 patients whom surgery was recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.	Candidates Whom Surgery is Not Recommended The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.
Progression Free Survival (PFS)-6	28.07 percentage of participants Interval 16.81 to 40.45	—

SECONDARY outcome

Timeframe: From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, up to 12 months

Population: Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 12 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-12 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 12 months after treatment.

Outcome measures

Measure	Candidates Whom Surgery is Recommended. n=30 Participants The first 6 patients whom surgery was recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.	Candidates Whom Surgery is Not Recommended The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.
Progression Free Survival (PFS)-12	16.84 percentage of participants Interval 7.84 to 28.75	—

SECONDARY outcome

Timeframe: From the time of exposure to study drug to death from any cause. If patient discontinued study drug, they were assessed the first 3 months after discontinuation, then every 3 months up to 1 year, then every 6 months thereafter until death.

Population: Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

To assess the effect of BBI608 + temozolomide (TMZ) on the overall survival of patients with recurrent or progressive glioblastoma multiforme (GBM) who had not received prior treatment with bevacizumab or other anti-vascular endothelial growth factor agents who either were eligible or not eligible for surgical resection.

Outcome measures

Measure	Candidates Whom Surgery is Recommended. n=30 Participants The first 6 patients whom surgery was recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.	Candidates Whom Surgery is Not Recommended The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.
Overall Survival (OS)	8.05 months Interval 6.01 to 10.87	—

SECONDARY outcome

Timeframe: 4 weeks

Population: Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

To assess the percentage of patients that had evaluable disease at baseline with a documented complete response, partial response, and stable disease (CR + PR + SD) based on the Response Assessment in Neuro-Oncology (RANO) criteria out of all patients who received at least one dose of any study drug and had evaluable disease at baseline.

Outcome measures

Measure	Candidates Whom Surgery is Recommended. n=30 Participants The first 6 patients whom surgery was recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.	Candidates Whom Surgery is Not Recommended The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.
Disease Control Rate (DCR)	30 percentage of patients Interval 14.7 to 49.4	—

SECONDARY outcome

Timeframe: 4 weeks

Population: Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients.

The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria.

Outcome measures

Measure	Candidates Whom Surgery is Recommended. n=30 Participants The first 6 patients whom surgery was recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.	Candidates Whom Surgery is Not Recommended The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.
Overall Response Rate (ORR)	3 percentage Interval 2.1 to 10.87	—

SECONDARY outcome

Timeframe: On Day 1 and Day 5 after the first dosing, prior to dosing and 1, 2, 3, 5, 5h40m (day 1 only), 6, 7, 8 and 24 hours after first dose of BBI608

Population: Candidates for who surgery was and was not recommended that received at least one dose of study drug and had at least one quantifiable concentration.

The area under the curve of BBI608, from time 0 to the last quantifiable concentration, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method)

Outcome measures

Measure	Candidates Whom Surgery is Recommended. n=4 Participants The first 6 patients whom surgery was recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.	Candidates Whom Surgery is Not Recommended n=10 Participants The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.
Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve	4820 h*ng/ml Geometric Coefficient of Variation 19	4200 h*ng/ml Geometric Coefficient of Variation 37.4

SECONDARY outcome

Timeframe: At the time of surgical resection

Population: Candidates whom surgery is either recommended or nor recommended that received 28 days of study drug and provided tissue samples.

Tumor samples to provide information of the biomarkers by histopathology and Cancer Stem Cell assays as well as the concentration of study drug in tumors.

Outcome measures

Measure	Candidates Whom Surgery is Recommended. n=23 Participants The first 6 patients whom surgery was recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.	Candidates Whom Surgery is Not Recommended The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis.
Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors pSTAT3+	19 Participants	—
Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors pSTAT3-	2 Participants	—
Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors Not Applicable	2 Participants	—

Adverse Events

Candidates Whom Surgery is Recommended

Serious events: 3 serious events

Other events: 4 other events

Deaths: 4 deaths

Candidates Whom Surgery is Not Recommended

Serious events: 5 serious events

Other events: 30 other events

Deaths: 22 deaths

Serious adverse events

Measure	Candidates Whom Surgery is Recommended n=4 participants at risk Participants whom surgery was recommended and received at least one dose of study medication (BBI608).	Candidates Whom Surgery is Not Recommended n=30 participants at risk Patients who were not candidates for surgical resection and received at least one dose of study medication (BBI608).
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Gastrointestinal disorders Vomiting	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Gastrointestinal disorders Colitis	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
General disorders Fatigue	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Pyramidal tract syndrome	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Seizure	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Cerebrospinal fluid leakage	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Aphasia	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Lethargy	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Status epilepticus	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Vascular disorders Deep vein thrombosis	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Infections and infestations Cellulitis	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Infections and infestations Postoperative wound infection	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Infections and infestations Wound infection	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Psychiatric disorders Confusional state	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.

Other adverse events

Measure	Candidates Whom Surgery is Recommended n=4 participants at risk Participants whom surgery was recommended and received at least one dose of study medication (BBI608).	Candidates Whom Surgery is Not Recommended n=30 participants at risk Patients who were not candidates for surgical resection and received at least one dose of study medication (BBI608).
Gastrointestinal disorders Diarrhoea	75.0% 3/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	90.0% 27/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Gastrointestinal disorders Abdominal pain	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	70.0% 21/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Gastrointestinal disorders Nausea	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	46.7% 14/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Gastrointestinal disorders Vomiting	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	33.3% 10/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Gastrointestinal disorders Constipation	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	16.7% 5/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Gastrointestinal disorders Dyspepsia	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	10.0% 3/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Headache	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	33.3% 10/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Pyramidal tract syndrome	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	16.7% 5/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Aphasia	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	13.3% 4/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Dysarthria	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	13.3% 4/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Hemiparesis	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	13.3% 4/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Cognitive disorder	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	10.0% 3/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Dizziness	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	10.0% 3/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Memory Impairment	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	10.0% 3/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Paraesthesia	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	10.0% 3/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Hemianopia homonymous	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Seizure	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Nervous system disorders Cerebrospinal fluid leakage	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
General disorders Fatigue	100.0% 4/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	53.3% 16/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
General disorders Gait disturbance	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	10.0% 3/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
General disorders Oedema peripheral	75.0% 3/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Investigations Lymphocyte count decreased	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	20.0% 6/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Investigations Platelet count decreased	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	20.0% 6/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Investigations Weight decreased	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	16.7% 5/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Investigations Alanine aminotransferase increased	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	13.3% 4/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Investigations Neutrophil count decreased	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	10.0% 3/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Investigations Aspartate aminotransferase increased	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Investigations Weight Increased	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Investigations White blood cell count decreased	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Metabolism and nutrition disorders Decreased appetite	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	20.0% 6/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Metabolism and nutrition disorders Hyperglycaemia	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	10.0% 3/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Psychiatric disorders Confusional state	75.0% 3/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Renal and urinary disorders Chromaturia	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	13.3% 4/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Vascular disorders Hypotension	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Infections and infestations Nasopharyngitis	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Injury, poisoning and procedural complications Fall	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	10.0% 3/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Injury, poisoning and procedural complications Contusion	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Blood and lymphatic system disorders Anaemia	25.0% 1/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Ear and labyrinth disorders Ear pain	0.00% 0/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	6.7% 2/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	0.00% 0/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	50.0% 2/4 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.	3.3% 1/30 • Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.

Additional Information

Connor Marshall

Sumitomo Dainippon Pharma Oncology

Phone: 843-364-8039

Email: cmarshall@bostonbiomedical.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60