A Japanese Phase 1 Trial of TH-302 in Subjects With Solid Tumors and Pancreatic Cancer

A Japanese Single Center, Open-label, Phase I Trial of TH-302 Given Intravenously to Subjects With Solid Tumors as Monotherapy or to Subjects With Advanced Pancreatic Cancer in Combination With Gemcitabine

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01833546

Enrollment

Registered

2013-04-17

Start date

2013-04-18

Completion date

2016-01-25

Last updated

2018-10-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Solid Tumor, Pancreatic Cancer

Keywords

Solid tumor, Pancreatic cancer, TH-302, Gemcitabine, Evofosfamide

Brief summary

This is a Japanese Phase 1, open-label, and dose-escalating trial of TH-302 as monotherapy in subjects with solid tumors and in combination with gemcitabine in subjects with pancreatic cancer.

Interventions

DRUGEvofosfamide

Evofosfamide infusion intravenously at an escalated dose of 240, 340 or 480 milligram per square meter (mg/m\^2) on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or withdrawal.

DRUGGemcitabine

Gemcitabine 1000 mg/m\^2 on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or withdrawal.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

* At least 20 years of age * Signed written informed consent form * Histologically or cytologically confirmed advanced or metastatic solid tumor previously treated with one or more standard treatment regimen(s) or for which no effective therapy is available * Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic adenocarcinoma previously untreated with chemotherapy or systemic therapy * Recovered from toxicities of prior anti-cancer treatment to Grade 1 or less * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy of at least 3 months * Acceptable liver function, renal function, hematologic status and coagulation status as defined in the protocol * No clinically significant abnormalities in urinalysis * Effective contraception for both male and female subjects if the risk of conception exists * Other inclusion criteria apply

Exclusion criteria

* Prior anti-cancer treatment with more than 3 myelosuppressive cytotoxic chemotherapy regimens * Prior treatment with gemcitabine for their advanced or metastatic pancreatic cancer, except for radiosensitizing doses of gemcitabine * Prior radiotherapy to more than 30 percent of the bone marrow within 6 months prior to the trial entry * Cardiac disease with New York Heart Association (NYHA) Class 3 or 4, within 6 months prior to the trial entry * Clinically significant (that is, active) cardiovascular disease * Seizure disorders requiring anticonvulsant therapy * Known brain, leptomeningeal or epidural metastases (unless previously treated and well controlled for at least 3 months at the trial entry) * Previously treated malignancies other than the current disease for at least 5 years at the trial entry * Severe chronic obstructive or other pulmonary disease major surgery, within 4 weeks prior to the trial entry, without complete recovery * Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy * Anti-cancer treatment prior to trial entry * Participation in an investigational drug or device trial within 4 weeks prior to the trial entry * Known infection with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C * A history of allergic reactions * Taking a medication that is either moderate or strong inhibitor or inducer of cytochrome P450 (CYP)3A4 or is a sensitive substrate of other cytochrome P450 * Pregnancy or lactation period * Concomitant disease or condition that could interfere with the conduct of the trial, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this trial * Unwillingness or inability to comply with the trial protocol for any reason * Legal incapacity or limited legal capacity * Other

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Who Experienced Any Dose-Limiting Toxicity (DLT) During First Cycle - Day 1 to 28	Day 1 up to Day 28 of Cycle 1	A DLT was defined as any of the following toxicities at any dose level that occurred during the first cycle, and were considered to be related to the study drug by the Investigator or the Sponsor: - Grade 3 or Grade 4 non-hematological toxicity, except for Grade 3 or Grade 4 nausea, vomiting and diarrhea, - Grade 3 or higher skin reactions or mucosal toxicities, - Febrile neutropenia, - Grade 3 alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation lasting more than 7 days, - Grade 4 neutropenia lasting more than 5 days, - Grade 4 thrombocytopenia, - Grade 4 anemia, - Any non-preexisting Grade 2 or higher non-hematologic toxicity which, in the judgment of the Investigator and the Sponsor, was considered a DLT, - Any Grade 2 or higher non-hematologic toxicity that did not resolve to Grade 0 or Grade 1 toxicity by the start of the next cycle which, in the judgment of the Investigator and the Sponsor, was considered a DLT.

Secondary

Measure	Time frame	Description
Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	—
Time to Reach Maximum Plasma Concentration (Tmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15	Tmax was the time to peak concentration in plasma, obtained directly from the concentration versus time curve. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.
Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Maximum observed plasma concentration was assessed.
Maximum Observed Plasma Concentration (Cmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15	Maximum observed Plasma concentration was assessed. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.
Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Terminal rate constant was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15	Terminal rate constant was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.
Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Terminal half-life was calculated as ln(2)/λz. Where λz is a Terminal rate constant, which was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
Apparent Terminal Half-life (t1/2) of of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15	Terminal half-life was calculated as ln(2)/λz. Where λz is a Terminal rate constant, which was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Area under the concentration-time curve from time 0 to the last quantifiable concentration was assessed.
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15	Area under the concentration-time curve from time 0 to the last quantifiable concentration was assessed. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Area under the concentration-time curve from time zero extrapolated to infinity, calculated as AUC(0-last) + last observed concentration (Clast)/terminal rate constant (λz), using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations. Where AUC(0-last) is area under the concentration-time curve from time 0 to the last quantifiable concentration was assessed. λz was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15	Area under the concentration-time curve from time zero extrapolated to infinity, calculated as AUC(0-last) + last observed concentration (Clast)/terminal rate constant (λz), using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations. Where AUC(0-last) is area under the concentration-time curve from time 0 to the last quantifiable concentration was assessed. λz was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.
Apparent Total Body Clearance of (CL) of Evofosfamide	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Apparent total clearance (CL/F) was calculated as dose divided by area under the plasma concentration-time profile from time zero extrapolated to infinity (AUC\[inf\]).
Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	Baseline up to 33 months	AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are events with start date on or after the date of first dose of study treatment and up to and including 30 days after the last dose of study treatment, or events with start date prior to the date of first dose of study treatment, and worsened in severity or become serious during treatment. TEAEs include both Serious TEAEs and non-serious TEAEs.
Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) was the apparent volume of distribution at steady-state.
Apparent Volume of Distribution at Steady State (Vss) of Gemcitabine	Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15	Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) was the apparent volume of distribution at steady-state. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.
Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by elimination rate constant \[λz\]) following single dose. Area under the plasma concentration-time curve from time zero to infinity, calculated (AUC0-inf) as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured plasma concentration is at or above lower limit of quantification (LLQ) and λz is the elimination rate constant. And the elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data.
Apparent Volume of Distribution During Terminal Phase (Vz) of Gemcitabine	Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15	Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by elimination rate constant \[λz\]) following single dose. Area under the plasma concentration-time curve from time zero to infinity, calculated (AUC0-inf) as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured plasma concentration is at or above lower limit of quantification (LLQ) and λz is the elimination rate constant. And the elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.
Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Cumulative amount excreted in urine from time zero to the end of the last measurable concentration was reported.
Renal Clearance (CL) for Evofosfamide	Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15	Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time.
Best Overall Response (BOR)	Time from first treatment to final assessment at 33 months	BOR was determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). BOR was defined as the best response of any of the confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) and progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Number of participants with CR, PR, SD and PD were reported.
Number of Participants With Objective Response	Time from first treatment to final assessment at 33 months	OR was determined according to RECIST v1.1. Objective response is defined as a best overall response of confirmed complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Number of participants with OR were reported.
Number of Participants With Disease Control	Time from first treatment to final assessment at 33 months	Disease Control was defined as having achieved at least disease stabilization; that is participants with confirmed CR, PR, or SD lasting for at least 16 weeks. CR: Disappearance of all target lesions. PR: A decrease of at least 30% in the sum of the longest diameter of target lesions. PD: PD is defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. SD: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events	Baseline up to 33 months	Clinical laboratory parameters that were assessed included: hematological parameters, blood chemistry parameters, coagulation and urinalysis and the vital signs that were assessed included: blood pressure, heart rate, respiratory rate, and body temperature.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as Treatment Emergent Adverse Events (TEAEs)	Baseline up to 33 months	Twelve-lead ECGs were performed and assessed after at least 5 minutes rest in supine position locally.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2	Baseline up to 33 months	ECOG performance status measured to assess subject's performance status on a scale of 0 to 5, where 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory (more than 50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=Death. Number of participants with ECOG performance status score of 2 or higher than 2 were reported.
Apparent Total Body Clearance of (CL) of Gemcitabine	Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15	Apparent total clearance (CL/F) was calculated as dose divided by area under the plasma concentration-time profile from time zero extrapolated to infinity (AUC\[inf\]). This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.

Countries

Japan

Participant flow

Recruitment details

First participant (informed consent): 18 April 2013. Study completion date: 25 January 2016.

Participants by arm

Arm	Count
Evofosfamide 240 mg Participants received evofosfamide infusion intravenously at a dose of 240 milligram per square meter (mg/m\^2) on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or participant withdrawal.	3
Evofosfamide 240 mg Participants received evofosfamide infusion intravenously at a dose of 240 milligram per square meter (mg/m\^2) on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or participant withdrawal.	3
Evofosfamide 340 mg Participants received evofosfamide infusion intravenously at a dose of 340 mg/m\^2 on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or participant withdrawal.	3
Evofosfamide 340 mg Participants received evofosfamide infusion intravenously at a dose of 340 mg/m\^2 on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or participant withdrawal.	3
Evofosfamide 480 mg Participants received evofosfamide infusion intravenously at a dose of 480 mg/m\^2 on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or participant withdrawal.	8
Evofosfamide 480 mg Participants received evofosfamide infusion intravenously at a dose of 480 mg/m\^2 on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or participant withdrawal.	8
Evofosfamide 340 mg + Gemcitabine Participants received 340 mg/m\^2 evofosfamide in combination with 1,000 mg/m\^2 gemcitabine intravenously on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or participant withdrawal.	6
Evofosfamide 340 mg + Gemcitabine Participants received 340 mg/m\^2 evofosfamide in combination with 1,000 mg/m\^2 gemcitabine intravenously on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or participant withdrawal.	6
Total	40

Baseline characteristics

Characteristic	Total	Evofosfamide 240 mg	Evofosfamide 340 mg	Evofosfamide 480 mg	Evofosfamide 340 mg + Gemcitabine
Age, Customized Greater than or equal to (>=) 65 years	10 Participants	1 Participants	2 Participants	4 Participants	3 Participants
Age, Customized Less than (<) 65 years	10 Participants	2 Participants	1 Participants	4 Participants	3 Participants
Sex: Female, Male Female	8 Participants	2 Participants	0 Participants	5 Participants	1 Participants
Sex: Female, Male Male	12 Participants	1 Participants	3 Participants	3 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 3	0 / 3	0 / 8	0 / 6
other Total, other adverse events	3 / 3	3 / 3	8 / 8	6 / 6
serious Total, serious adverse events	0 / 3	0 / 3	1 / 8	1 / 6

Outcome results

Primary

Number of Participants Who Experienced Any Dose-Limiting Toxicity (DLT) During First Cycle - Day 1 to 28

A DLT was defined as any of the following toxicities at any dose level that occurred during the first cycle, and were considered to be related to the study drug by the Investigator or the Sponsor: - Grade 3 or Grade 4 non-hematological toxicity, except for Grade 3 or Grade 4 nausea, vomiting and diarrhea, - Grade 3 or higher skin reactions or mucosal toxicities, - Febrile neutropenia, - Grade 3 alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation lasting more than 7 days, - Grade 4 neutropenia lasting more than 5 days, - Grade 4 thrombocytopenia, - Grade 4 anemia, - Any non-preexisting Grade 2 or higher non-hematologic toxicity which, in the judgment of the Investigator and the Sponsor, was considered a DLT, - Any Grade 2 or higher non-hematologic toxicity that did not resolve to Grade 0 or Grade 1 toxicity by the start of the next cycle which, in the judgment of the Investigator and the Sponsor, was considered a DLT.

Time frame: Day 1 up to Day 28 of Cycle 1

Population: The DLT Analysis Set included all participants who experienced a DLT during Cycle 1 or who did not experience a DLT, completed Cycle 1 and received 90% or more of all planned total dose of evofosfamide, and gemcitabine for the combination, during Cycle 1.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Evofosfamide 240 mg	Number of Participants Who Experienced Any Dose-Limiting Toxicity (DLT) During First Cycle - Day 1 to 28	0 Participants
Evofosfamide 340 mg	Number of Participants Who Experienced Any Dose-Limiting Toxicity (DLT) During First Cycle - Day 1 to 28	0 Participants
Evofosfamide 480 mg	Number of Participants Who Experienced Any Dose-Limiting Toxicity (DLT) During First Cycle - Day 1 to 28	1 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants Who Experienced Any Dose-Limiting Toxicity (DLT) During First Cycle - Day 1 to 28	0 Participants

Secondary

Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Time frame: Monotherapy: pre-dose, 0.25, 0.5, 0.58, 0.75, 1, 1.08, 1.25, 1.5, 2, 2.5, 3.5, 4.5, 6.5, 8.5, 12.5 hours post-dose on Day 1 and 15; Combination therapy: pre-dose, 0.5, 0.66, 1, 2, 2.5, 3, 3.5, 4, 4.5, 6.5, 8, 10.5, 26.5 hours post-dose on Day 1 and 15

Population: The PK Analysis Set. Here Number Analyzed signifies those participants who were evaluated at the specified time point. There were no participants analyzed at certain time points (that is, Number Analyzed = 0) because there was no data collected for respective arms at those time points.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	0.4691 hours	—
Evofosfamide 240 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	0.6850 hours	Geometric Coefficient of Variation 6
Evofosfamide 240 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	0.4153 hours	—
Evofosfamide 240 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	0.6881 hours	Geometric Coefficient of Variation 6.2
Evofosfamide 340 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	0.2566 hours	Geometric Coefficient of Variation 35.7
Evofosfamide 340 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	0.2846 hours	—
Evofosfamide 340 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	0.6716 hours	Geometric Coefficient of Variation 2.5
Evofosfamide 340 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	0.6304 hours	Geometric Coefficient of Variation 12.3
Evofosfamide 480 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	0.4384 hours	Geometric Coefficient of Variation 19.5
Evofosfamide 480 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	0.6334 hours	Geometric Coefficient of Variation 6
Evofosfamide 480 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	0.7285 hours	Geometric Coefficient of Variation 27
Evofosfamide 480 mg	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	0.3942 hours	Geometric Coefficient of Variation 18.8
Evofosfamide 340 mg + Gemcitabine	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	0.5889 hours	Geometric Coefficient of Variation 6
Evofosfamide 340 mg + Gemcitabine	Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	0.6049 hours	Geometric Coefficient of Variation 10.3

Secondary

Apparent Terminal Half-life (t1/2) of of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Terminal half-life was calculated as ln(2)/λz. Where λz is a Terminal rate constant, which was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15

Population: The PK Analysis Set included all participants who received at least 1 dose of gemcitabine (that is, actual total dose of gemcitabine \> 0) and who provided sufficient data for a concentration-time profile for gemcitabine. Here Number Analyzed signifies those participants who were evaluated at the specified time point.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Apparent Terminal Half-life (t1/2) of of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 1	0.2139 hours	Geometric Coefficient of Variation 9.6
Evofosfamide 240 mg	Apparent Terminal Half-life (t1/2) of of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 15	0.2186 hours	Geometric Coefficient of Variation 9.9
Evofosfamide 240 mg	Apparent Terminal Half-life (t1/2) of of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 1	7.741 hours	Geometric Coefficient of Variation 45.4
Evofosfamide 240 mg	Apparent Terminal Half-life (t1/2) of of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 15	7.964 hours	Geometric Coefficient of Variation 54

Secondary

Apparent Total Body Clearance of (CL) of Evofosfamide

Apparent total clearance (CL/F) was calculated as dose divided by area under the plasma concentration-time profile from time zero extrapolated to infinity (AUC\[inf\]).

Population: The PK Analysis Set included all participants who received at least 1 dose of evofosfamide (that is, actual total dose of evofosfamide \> 0) and who provided sufficient data for a concentration-time profile for evofosfamide. Here Number Analyzed signifies those participants who were evaluated at the specified time point.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Apparent Total Body Clearance of (CL) of Evofosfamide	Evofosfamide: Day 1	45.83 Liter per hour per square meter	Geometric Coefficient of Variation 8
Evofosfamide 240 mg	Apparent Total Body Clearance of (CL) of Evofosfamide	Evofosfamide: Day 15	45.74 Liter per hour per square meter	Geometric Coefficient of Variation 1.5
Evofosfamide 340 mg	Apparent Total Body Clearance of (CL) of Evofosfamide	Evofosfamide: Day 15	41.74 Liter per hour per square meter	Geometric Coefficient of Variation 18
Evofosfamide 340 mg	Apparent Total Body Clearance of (CL) of Evofosfamide	Evofosfamide: Day 1	43.05 Liter per hour per square meter	Geometric Coefficient of Variation 13.1
Evofosfamide 480 mg	Apparent Total Body Clearance of (CL) of Evofosfamide	Evofosfamide: Day 1	46.07 Liter per hour per square meter	Geometric Coefficient of Variation 14.6
Evofosfamide 480 mg	Apparent Total Body Clearance of (CL) of Evofosfamide	Evofosfamide: Day 15	44.59 Liter per hour per square meter	Geometric Coefficient of Variation 17.7
Evofosfamide 340 mg + Gemcitabine	Apparent Total Body Clearance of (CL) of Evofosfamide	Evofosfamide: Day 1	56.23 Liter per hour per square meter	Geometric Coefficient of Variation 11.8
Evofosfamide 340 mg + Gemcitabine	Apparent Total Body Clearance of (CL) of Evofosfamide	Evofosfamide: Day 15	60.43 Liter per hour per square meter	Geometric Coefficient of Variation 21

Secondary

Apparent Total Body Clearance of (CL) of Gemcitabine

Apparent total clearance (CL/F) was calculated as dose divided by area under the plasma concentration-time profile from time zero extrapolated to infinity (AUC\[inf\]). This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Apparent Total Body Clearance of (CL) of Gemcitabine	Gemcitabine: Day 1	93.29 Liter per hour per square meter	Geometric Coefficient of Variation 24.5
Evofosfamide 240 mg	Apparent Total Body Clearance of (CL) of Gemcitabine	Gemcitabine: Day 15	101.04 Liter per hour per square meter	Geometric Coefficient of Variation 1.9

Secondary

Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) was the apparent volume of distribution at steady-state.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide	Evofosfamide: Day 1	21.71 Liter per square meter	Geometric Coefficient of Variation 15
Evofosfamide 240 mg	Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide	Evofosfamide: Day 15	20.26 Liter per square meter	Geometric Coefficient of Variation 16.4
Evofosfamide 340 mg	Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide	Evofosfamide: Day 15	18.83 Liter per square meter	Geometric Coefficient of Variation 9.6
Evofosfamide 340 mg	Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide	Evofosfamide: Day 1	21.54 Liter per square meter	Geometric Coefficient of Variation 2.4
Evofosfamide 480 mg	Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide	Evofosfamide: Day 1	21.79 Liter per square meter	Geometric Coefficient of Variation 15.2
Evofosfamide 480 mg	Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide	Evofosfamide: Day 15	21.35 Liter per square meter	Geometric Coefficient of Variation 5.2
Evofosfamide 340 mg + Gemcitabine	Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide	Evofosfamide: Day 1	39.03 Liter per square meter	Geometric Coefficient of Variation 7.1
Evofosfamide 340 mg + Gemcitabine	Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide	Evofosfamide: Day 15	41.55 Liter per square meter	Geometric Coefficient of Variation 9

Secondary

Apparent Volume of Distribution at Steady State (Vss) of Gemcitabine

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Apparent Volume of Distribution at Steady State (Vss) of Gemcitabine	Gemcitabine: Day 1	34.41 Liter per square meter	Geometric Coefficient of Variation 21.9
Evofosfamide 240 mg	Apparent Volume of Distribution at Steady State (Vss) of Gemcitabine	Gemcitabine: Day 15	43.71 Liter per square meter	Geometric Coefficient of Variation 18.3

Secondary

Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide

Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by elimination rate constant \[λz\]) following single dose. Area under the plasma concentration-time curve from time zero to infinity, calculated (AUC0-inf) as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured plasma concentration is at or above lower limit of quantification (LLQ) and λz is the elimination rate constant. And the elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide	Evofosfamide: Day 1	44.85 Liter per square meter	Geometric Coefficient of Variation 10.3
Evofosfamide 240 mg	Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide	Evofosfamide: Day 15	45.41 Liter per square meter	Geometric Coefficient of Variation 5.3
Evofosfamide 340 mg	Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide	Evofosfamide: Day 15	40.44 Liter per square meter	Geometric Coefficient of Variation 17.5
Evofosfamide 340 mg	Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide	Evofosfamide: Day 1	39.16 Liter per square meter	Geometric Coefficient of Variation 1.2
Evofosfamide 480 mg	Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide	Evofosfamide: Day 1	42.10 Liter per square meter	Geometric Coefficient of Variation 15.3
Evofosfamide 480 mg	Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide	Evofosfamide: Day 15	46.86 Liter per square meter	Geometric Coefficient of Variation 19.5
Evofosfamide 340 mg + Gemcitabine	Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide	Evofosfamide: Day 1	49.07 Liter per square meter	Geometric Coefficient of Variation 11.4
Evofosfamide 340 mg + Gemcitabine	Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide	Evofosfamide: Day 15	51.34 Liter per square meter	Geometric Coefficient of Variation 17.3

Secondary

Apparent Volume of Distribution During Terminal Phase (Vz) of Gemcitabine

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Apparent Volume of Distribution During Terminal Phase (Vz) of Gemcitabine	Gemcitabine: Day 1	28.78 Liter per square meter	Geometric Coefficient of Variation 29.8
Evofosfamide 240 mg	Apparent Volume of Distribution During Terminal Phase (Vz) of Gemcitabine	Gemcitabine: Day 15	30.14 Liter per square meter	Geometric Coefficient of Variation 1.2

Secondary

Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Area under the concentration-time curve from time 0 to the last quantifiable concentration was assessed.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	5266.9 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 8.3
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	5232.4 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 2.4
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	38.1 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 41.1
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	41.4 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 24.3
Evofosfamide 340 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	8191.1 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 17.8
Evofosfamide 340 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	61.7 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 84.4
Evofosfamide 340 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	101.2 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 18.6
Evofosfamide 340 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	7864.2 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 13
Evofosfamide 480 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	153.8 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 25
Evofosfamide 480 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	10742.8 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 16.7
Evofosfamide 480 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	149.4 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 23.6
Evofosfamide 480 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	10416.1 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 14.4
Evofosfamide 340 mg + Gemcitabine	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	77.0 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 23.6
Evofosfamide 340 mg + Gemcitabine	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	5616.4 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 21
Evofosfamide 340 mg + Gemcitabine	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	5989.5 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 11.5
Evofosfamide 340 mg + Gemcitabine	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	47.7 nghour per mL (nghour/mL)	Geometric Coefficient of Variation 66.5

Secondary

Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Area under the concentration-time curve from time 0 to the last quantifiable concentration was assessed. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 1	10001.2 ng*hour/mL	Geometric Coefficient of Variation 21.8
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 15	9576.0 ng*hour/mL	Geometric Coefficient of Variation 7.2
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 1	139397.1 ng*hour/mL	Geometric Coefficient of Variation 25.1
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 15	116487.7 ng*hour/mL	Geometric Coefficient of Variation 28.6

Secondary

Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Area under the concentration-time curve from time zero extrapolated to infinity, calculated as AUC(0-last) + last observed concentration (Clast)/terminal rate constant (λz), using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations. Where AUC(0-last) is area under the concentration-time curve from time 0 to the last quantifiable concentration was assessed. λz was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	90 ng*hour/mL	—
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	5296.2 ng*hour/mL	Geometric Coefficient of Variation 8.2
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	51 ng*hour/mL	—
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	5261.3 ng*hour/mL	Geometric Coefficient of Variation 2.4
Evofosfamide 340 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	115.1 ng*hour/mL	Geometric Coefficient of Variation 17.2
Evofosfamide 340 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	105 ng*hour/mL	—
Evofosfamide 340 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	8233.3 ng*hour/mL	Geometric Coefficient of Variation 18
Evofosfamide 340 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	7904.7 ng*hour/mL	Geometric Coefficient of Variation 13.2
Evofosfamide 480 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	171.8 ng*hour/mL	Geometric Coefficient of Variation 16.8
Evofosfamide 480 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	10459.6 ng*hour/mL	Geometric Coefficient of Variation 14.5
Evofosfamide 480 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	10786.6 ng*hour/mL	Geometric Coefficient of Variation 16.8
Evofosfamide 480 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	174.6 ng*hour/mL	Geometric Coefficient of Variation 21.9
Evofosfamide 340 mg + Gemcitabine	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	5664.9 ng*hour/mL	Geometric Coefficient of Variation 21.3
Evofosfamide 340 mg + Gemcitabine	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	6049.5 ng*hour/mL	Geometric Coefficient of Variation 11.9

Secondary

Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 1	10719.5 ng*hour/mL	Geometric Coefficient of Variation 24.5
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 15	9996.0 ng*hour/mL	Geometric Coefficient of Variation 1.3
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 1	159014.1 ng*hour/mL	Geometric Coefficient of Variation 35.3
Evofosfamide 240 mg	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 15	133203.0 ng*hour/mL	Geometric Coefficient of Variation 46.3

Secondary

Best Overall Response (BOR)

BOR was determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). BOR was defined as the best response of any of the confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) and progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Number of participants with CR, PR, SD and PD were reported.

Time frame: Time from first treatment to final assessment at 33 months

Population: Efficacy Analysis Set included all participants who received at least 1 planned dose of evofosfamide and who had a baseline tumor assessment and at least 1 tumor assessment according to RECIST version 1.1 after the first dose of study drug.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Evofosfamide 240 mg	Best Overall Response (BOR)	Complete Response	0 Participants
Evofosfamide 240 mg	Best Overall Response (BOR)	Partial Response	0 Participants
Evofosfamide 240 mg	Best Overall Response (BOR)	Stable Disease	0 Participants
Evofosfamide 240 mg	Best Overall Response (BOR)	Progressive Disease	2 Participants
Evofosfamide 340 mg	Best Overall Response (BOR)	Partial Response	0 Participants
Evofosfamide 340 mg	Best Overall Response (BOR)	Stable Disease	0 Participants
Evofosfamide 340 mg	Best Overall Response (BOR)	Progressive Disease	3 Participants
Evofosfamide 340 mg	Best Overall Response (BOR)	Complete Response	0 Participants
Evofosfamide 480 mg	Best Overall Response (BOR)	Stable Disease	2 Participants
Evofosfamide 480 mg	Best Overall Response (BOR)	Partial Response	0 Participants
Evofosfamide 480 mg	Best Overall Response (BOR)	Progressive Disease	4 Participants
Evofosfamide 480 mg	Best Overall Response (BOR)	Complete Response	0 Participants
Evofosfamide 340 mg + Gemcitabine	Best Overall Response (BOR)	Progressive Disease	3 Participants
Evofosfamide 340 mg + Gemcitabine	Best Overall Response (BOR)	Partial Response	0 Participants
Evofosfamide 340 mg + Gemcitabine	Best Overall Response (BOR)	Complete Response	0 Participants
Evofosfamide 340 mg + Gemcitabine	Best Overall Response (BOR)	Stable Disease	2 Participants

Secondary

Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)

Cumulative amount excreted in urine from time zero to the end of the last measurable concentration was reported.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)	Evofosfamide: Day 1	22.913 milligram per square meter	Geometric Coefficient of Variation 43.6
Evofosfamide 240 mg	Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)	Evofosfamide: Day 15	11.674 milligram per square meter	Geometric Coefficient of Variation 139.2
Evofosfamide 340 mg	Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)	Evofosfamide: Day 15	22.605 milligram per square meter	Geometric Coefficient of Variation 53.7
Evofosfamide 340 mg	Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)	Evofosfamide: Day 1	17.135 milligram per square meter	Geometric Coefficient of Variation 66.6
Evofosfamide 480 mg	Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)	Evofosfamide: Day 1	38.771 milligram per square meter	Geometric Coefficient of Variation 33.3
Evofosfamide 480 mg	Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)	Evofosfamide: Day 15	40.049 milligram per square meter	Geometric Coefficient of Variation 66
Evofosfamide 340 mg + Gemcitabine	Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)	Evofosfamide: Day 1	22.691 milligram per square meter	Geometric Coefficient of Variation 82
Evofosfamide 340 mg + Gemcitabine	Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)	Evofosfamide: Day 15	30.025 milligram per square meter	Geometric Coefficient of Variation 31.6

Secondary

Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Maximum observed plasma concentration was assessed.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	6502.3 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 29.8
Evofosfamide 240 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	63.37 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 32.7
Evofosfamide 240 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	62.01 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 30.7
Evofosfamide 240 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	7159.9 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 5.3
Evofosfamide 340 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	103.74 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 64.8
Evofosfamide 340 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	10248.2 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 5.9
Evofosfamide 340 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	10009.8 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 8.4
Evofosfamide 340 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	149.36 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 11.2
Evofosfamide 480 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	14661.2 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 9.9
Evofosfamide 480 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	224.95 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 25.4
Evofosfamide 480 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	14016.7 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 14.5
Evofosfamide 480 mg	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	207.88 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 22
Evofosfamide 340 mg + Gemcitabine	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	8720.8 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 12.8
Evofosfamide 340 mg + Gemcitabine	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	124.92 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 33.5
Evofosfamide 340 mg + Gemcitabine	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	86.55 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 58.3
Evofosfamide 340 mg + Gemcitabine	Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	9303.4 Nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 7.2

Secondary

Maximum Observed Plasma Concentration (Cmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Maximum observed Plasma concentration was assessed. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15

Population: The PK Analysis Set included all Participants who received at least 1 dose of gemcitabine (that is, actual total dose of gemcitabine \> 0) and who provided sufficient data for a concentration-time profile for gemcitabine. Here Number Analyzed signifies those Participants who were evaluated at the specified time point.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Maximum Observed Plasma Concentration (Cmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 1	22596.2 ng/mL	Geometric Coefficient of Variation 22.3
Evofosfamide 240 mg	Maximum Observed Plasma Concentration (Cmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 15	21355.5 ng/mL	Geometric Coefficient of Variation 4
Evofosfamide 240 mg	Maximum Observed Plasma Concentration (Cmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 1	33923.9 ng/mL	Geometric Coefficient of Variation 23.1
Evofosfamide 240 mg	Maximum Observed Plasma Concentration (Cmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 15	33631.4 ng/mL	Geometric Coefficient of Variation 22.6

Secondary

Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as Treatment Emergent Adverse Events (TEAEs)

Twelve-lead ECGs were performed and assessed after at least 5 minutes rest in supine position locally.

Time frame: Baseline up to 33 months

Population: Safety population included all participants who received at least 1 dose of the study drug (evofosfamide or gemcitabine).

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Evofosfamide 240 mg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as Treatment Emergent Adverse Events (TEAEs)	0 Participants
Evofosfamide 340 mg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as Treatment Emergent Adverse Events (TEAEs)	0 Participants
Evofosfamide 480 mg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as Treatment Emergent Adverse Events (TEAEs)	3 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as Treatment Emergent Adverse Events (TEAEs)	1 Participants

Secondary

Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events

Clinical laboratory parameters that were assessed included: hematological parameters, blood chemistry parameters, coagulation and urinalysis and the vital signs that were assessed included: blood pressure, heart rate, respiratory rate, and body temperature.

Time frame: Baseline up to 33 months

Population: Safety population included all participants who received at least 1 dose of the study drug (evofosfamide or gemcitabine).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Evofosfamide 240 mg	Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events	Subjects with Lab Abnormalities	3 Participants
Evofosfamide 240 mg	Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events	Subjects with Vital signs Abnormalities	0 Participants
Evofosfamide 340 mg	Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events	Subjects with Vital signs Abnormalities	0 Participants
Evofosfamide 340 mg	Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events	Subjects with Lab Abnormalities	3 Participants
Evofosfamide 480 mg	Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events	Subjects with Lab Abnormalities	8 Participants
Evofosfamide 480 mg	Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events	Subjects with Vital signs Abnormalities	0 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events	Subjects with Lab Abnormalities	6 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events	Subjects with Vital signs Abnormalities	0 Participants

Secondary

Number of Participants With Disease Control

Disease Control was defined as having achieved at least disease stabilization; that is participants with confirmed CR, PR, or SD lasting for at least 16 weeks. CR: Disappearance of all target lesions. PR: A decrease of at least 30% in the sum of the longest diameter of target lesions. PD: PD is defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. SD: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

Time frame: Time from first treatment to final assessment at 33 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Evofosfamide 240 mg	Number of Participants With Disease Control	0 Participants
Evofosfamide 340 mg	Number of Participants With Disease Control	0 Participants
Evofosfamide 480 mg	Number of Participants With Disease Control	2 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants With Disease Control	2 Participants

Secondary

Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2

ECOG performance status measured to assess subject's performance status on a scale of 0 to 5, where 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory (more than 50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=Death. Number of participants with ECOG performance status score of 2 or higher than 2 were reported.

Time frame: Baseline up to 33 months

Population: Safety population included all participants who received at least 1 dose of the study drug (evofosfamide or gemcitabine).

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Evofosfamide 240 mg	Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2	0 Participants
Evofosfamide 340 mg	Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2	0 Participants
Evofosfamide 480 mg	Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2	1 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2	0 Participants

Secondary

Number of Participants With Objective Response

OR was determined according to RECIST v1.1. Objective response is defined as a best overall response of confirmed complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Number of participants with OR were reported.

Time frame: Time from first treatment to final assessment at 33 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Evofosfamide 240 mg	Number of Participants With Objective Response	0 Participants
Evofosfamide 340 mg	Number of Participants With Objective Response	0 Participants
Evofosfamide 480 mg	Number of Participants With Objective Response	0 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants With Objective Response	0 Participants

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death

AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are events with start date on or after the date of first dose of study treatment and up to and including 30 days after the last dose of study treatment, or events with start date prior to the date of first dose of study treatment, and worsened in severity or become serious during treatment. TEAEs include both Serious TEAEs and non-serious TEAEs.

Time frame: Baseline up to 33 months

Population: Safety population included all participants who received at least 1 dose of the study drug (evofosfamide or gemcitabine).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Evofosfamide 240 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	TEAEs	3 Participants
Evofosfamide 240 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	TEAEs leading to death	0 Participants
Evofosfamide 240 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	Serious TEAEs	0 Participants
Evofosfamide 340 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	TEAEs	3 Participants
Evofosfamide 340 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	TEAEs leading to death	0 Participants
Evofosfamide 340 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	Serious TEAEs	0 Participants
Evofosfamide 480 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	Serious TEAEs	1 Participants
Evofosfamide 480 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	TEAEs	8 Participants
Evofosfamide 480 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	TEAEs leading to death	0 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	TEAEs	6 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	TEAEs leading to death	0 Participants
Evofosfamide 340 mg + Gemcitabine	Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death	Serious TEAEs	1 Participants

Secondary

Renal Clearance (CL) for Evofosfamide

Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Renal Clearance (CL) for Evofosfamide	Evofosfamide: Day 1	4.35 Liter per hour per square meter	Geometric Coefficient of Variation 41.4
Evofosfamide 240 mg	Renal Clearance (CL) for Evofosfamide	Evofosfamide: Day 15	2.23 Liter per hour per square meter	Geometric Coefficient of Variation 137
Evofosfamide 340 mg	Renal Clearance (CL) for Evofosfamide	Evofosfamide: Day 15	2.76 Liter per hour per square meter	Geometric Coefficient of Variation 76.4
Evofosfamide 340 mg	Renal Clearance (CL) for Evofosfamide	Evofosfamide: Day 1	2.18 Liter per hour per square meter	Geometric Coefficient of Variation 59.9
Evofosfamide 480 mg	Renal Clearance (CL) for Evofosfamide	Evofosfamide: Day 1	3.72 Liter per hour per square meter	Geometric Coefficient of Variation 34.4
Evofosfamide 480 mg	Renal Clearance (CL) for Evofosfamide	Evofosfamide: Day 15	3.73 Liter per hour per square meter	Geometric Coefficient of Variation 83.1
Evofosfamide 340 mg + Gemcitabine	Renal Clearance (CL) for Evofosfamide	Evofosfamide: Day 1	3.79 Liter per hour per square meter	Geometric Coefficient of Variation 81.4
Evofosfamide 340 mg + Gemcitabine	Renal Clearance (CL) for Evofosfamide	Evofosfamide: Day 15	5.35 Liter per hour per square meter	Geometric Coefficient of Variation 15.4

Secondary

Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Terminal rate constant was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.

Population: The PK Analysis Set. Here Number Analyzed signifies those Participants who were evaluated at the specified time point. There were no Participants analyzed at certain time points (that is, Number Analyzed = 0) because there was no data collected for respective arms at those time points.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	1.478 Per hour	—
Evofosfamide 240 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	1.012 Per hour	Geometric Coefficient of Variation 6
Evofosfamide 240 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	1.669 Per hour	—
Evofosfamide 240 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	1.007 Per hour	Geometric Coefficient of Variation 6.2
Evofosfamide 340 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	2.701 Per hour	Geometric Coefficient of Variation 35.7
Evofosfamide 340 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	2.436 Per hour	—
Evofosfamide 340 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	1.032 Per hour	Geometric Coefficient of Variation 2.5
Evofosfamide 340 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	1.100 Per hour	Geometric Coefficient of Variation 12.3
Evofosfamide 480 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	1.581 Per hour	Geometric Coefficient of Variation 19.5
Evofosfamide 480 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	1.094 Per hour	Geometric Coefficient of Variation 6
Evofosfamide 480 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	0.951 Per hour	Geometric Coefficient of Variation 27
Evofosfamide 480 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	1.758 Per hour	Geometric Coefficient of Variation 18.8
Evofosfamide 340 mg + Gemcitabine	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	1.177 Per hour	Geometric Coefficient of Variation 6
Evofosfamide 340 mg + Gemcitabine	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	1.146 Per hour	Geometric Coefficient of Variation 10.3

Secondary

Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Terminal rate constant was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Evofosfamide 240 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 1	3.241 Per hour	Geometric Coefficient of Variation 9.6
Evofosfamide 240 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 15	3.171 Per hour	Geometric Coefficient of Variation 9.9
Evofosfamide 240 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 1	0.0895 Per hour	Geometric Coefficient of Variation 45.4
Evofosfamide 240 mg	Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 15	0.0870 Per hour	Geometric Coefficient of Variation 54

Secondary

Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Population: The Pharmacokinetics (PK) Analysis Set included all participants who received at least 1 dose of evofosfamide (that is, actual total dose of evofosfamide \> 0) and who provided sufficient data for a concentration-time profile for evofosfamide. Here Number Analyzed signifies those participants who were evaluated at the specified time point.

Arm	Measure	Group	Value (MEDIAN)
Evofosfamide 240 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	0.550 hours
Evofosfamide 240 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	0.550 hours
Evofosfamide 240 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	0.600 hours
Evofosfamide 240 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	0.22 hours
Evofosfamide 340 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	0.633 hours
Evofosfamide 340 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	0.533 hours
Evofosfamide 340 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	0.250 hours
Evofosfamide 340 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	0.550 hours
Evofosfamide 480 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	0.267 hours
Evofosfamide 480 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	0.575 hours
Evofosfamide 480 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	0.392 hours
Evofosfamide 480 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	0.567 hours
Evofosfamide 340 mg + Gemcitabine	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 15	0.533 hours
Evofosfamide 340 mg + Gemcitabine	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 15	0.533 hours
Evofosfamide 340 mg + Gemcitabine	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Br-IPM: Day 1	0.567 hours
Evofosfamide 340 mg + Gemcitabine	Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])	Evofosfamide: Day 1	0.550 hours

Secondary

Time to Reach Maximum Plasma Concentration (Tmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Tmax was the time to peak concentration in plasma, obtained directly from the concentration versus time curve. This outcome was applicable for only combination arm in which evofosfamide was administered along with gemcitabine.

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and 15

Arm	Measure	Group	Value (MEDIAN)
Evofosfamide 240 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 1	0.500 hours
Evofosfamide 240 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	Gemcitabine: Day 15	0.500 hours
Evofosfamide 240 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 1	0.500 hours
Evofosfamide 240 mg	Time to Reach Maximum Plasma Concentration (Tmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])	dFdU: Day 15	0.500 hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

A Japanese Phase 1 Trial of TH-302 in Subjects With Solid Tumors and Pancreatic Cancer

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Study design

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Exclusion criteria

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Primary

Secondary

Countries

Participant flow

Recruitment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Number of Participants Who Experienced Any Dose-Limiting Toxicity (DLT) During First Cycle - Day 1 to 28

Apparent Terminal Half-life (t1/2) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Apparent Terminal Half-life (t1/2) of of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Apparent Total Body Clearance of (CL) of Evofosfamide

Apparent Total Body Clearance of (CL) of Gemcitabine

Apparent Volume of Distribution at Steady State (Vss) of Evofosfamide

Apparent Volume of Distribution at Steady State (Vss) of Gemcitabine

Apparent Volume of Distribution During Terminal Phase (Vz) of Evofosfamide

Apparent Volume of Distribution During Terminal Phase (Vz) of Gemcitabine

Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Sampling Time With Concentration at or Above the Lower Limit of Quantitation (AUC[0-t]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Best Overall Response (BOR)

Cumulative Amount of Evofosfamide Excreted From Time Zero to Time After Dosing (Ae0-t)

Maximum Observed Plasma Concentration (Cmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Maximum Observed Plasma Concentration (Cmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as Treatment Emergent Adverse Events (TEAEs)

Number of Participants With Clinical Significant Laboratory Abnormalities and Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events

Number of Participants With Disease Control

Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2

Number of Participants With Objective Response

Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Death

Renal Clearance (CL) for Evofosfamide

Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Terminal Rate Constant Associated With the Terminal Elimination Phase (λz) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])

Time to Reach Maximum Plasma Concentration (Tmax) of Evofosfamide and Its Metabolite (Bromo-isophosphoramide Mustard [Br-IPM])

Time to Reach Maximum Plasma Concentration (Tmax) of Gemcitabine and Its Metabolite (2',2'-Difluorodeoxyuridine [dFdU])