Trial Outcomes & Findings for Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC (NCT NCT02047344)

NCT ID: NCT02047344

Last Updated: 2019-12-26

Results Overview

Tumor response will be assessed at 6 week intervals during the first treatment cycle using the RECIST criteria, version 1.1. Each patient will be assigned one of the following categories: 1) complete response (CR), 2) partial response (PR), 3) stable disease (SD), or 4) progressive disease (PD). Patients who died from any cause or discontinued the study for any reason without a post screening or Week 12 tumor assessment will be considered as failing to respond to treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

12 weeks

Results posted on

2019-12-26

Participant Flow

Unselected KRAS-positive and KRAS-negative patients with stage IV (including pleural effusion) non squamous NSCLC and radiologically-confirmed disease progression following greater than or equal to two, but less than or equal to four, prior lines of systemic anti cancer therapy.

Written informed consent was obtained from all patients before initiating screening. The screening period was up to 42 days in duration (Days 42 to 1) for K-Ras testing result, if no history k-Ras result.

Participant milestones

Participant milestones
Measure	K-Ras Negative Fresh or archival biopsy tissue to determine KRAS is not mutant.	K- Ras Mutant Fresh or archival biopsy tissue to determine KRAS is mutant.
Overall Study STARTED	16	15
Overall Study COMPLETED	16	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	K-Ras Negative n=15 Participants Fresh or archival biopsy tissue to determine KRAS is not mutant. Patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression.	K- Ras Mutant n=15 Participants Fresh or archival biopsy tissue to determine KRAS is mutant. Patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression.	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Asian	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment United States	7 Participants n=5 Participants	14 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Taiwan	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
ECOG performance status Fully active	10 Participants n=5 Participants	1 Participants n=7 Participants	11 Participants n=5 Participants
ECOG performance status Restricted in physically strenuous activity	4 Participants n=5 Participants	12 Participants n=7 Participants	16 Participants n=5 Participants
ECOG performance status Capable of all selfcare more than 50% work	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Defined as the proportion of patients alive and progression free at Week 12.

Outcome measures

Outcome measures
Measure	Progression-free Survival Rate/KRAS Negative Group n=15 Participants 200mg TID for treating KRAS negative patients 12 weeks	Progression-free Survival Rate/KRAS Mutant Group n=15 Participants 200mg TID for treating KRAS negative patients 12 weeks	Two Lines Failed Prior Chemotherapies Patients join with two lines failed prior chemotherapies	More Than Two Lines Failed Prior Chemotherapies patient failed more than two line chemotherapies before join.
Progression Free Survival Rate	4 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 8 hours

Population: There were 22 patients with reported concentration data who were eligible for the PK population.

PK sampling will be performed on Days 0 and 28 in all patients enrolled in Stage 1.PK endpoints will be derived for intensively sampled PK profiles by non compartmental methods and include: Cmax: peak concentration;Ctrough: trough plasma concentration.

Outcome measures

Outcome measures
Measure	Progression-free Survival Rate/KRAS Negative Group n=22 Participants 200mg TID for treating KRAS negative patients 12 weeks	Progression-free Survival Rate/KRAS Mutant Group n=22 Participants 200mg TID for treating KRAS negative patients 12 weeks	Two Lines Failed Prior Chemotherapies Patients join with two lines failed prior chemotherapies	More Than Two Lines Failed Prior Chemotherapies patient failed more than two line chemotherapies before join.
Cmax	276.87 ng/mL Standard Deviation 211.162	393.55 ng/mL Standard Deviation 315.434	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: 26 patients can be run the full analysis

the proportion of patients with a documented CR, PR and SD during the first 12 week treatment cycle according to RECIST version 1.1.

Outcome measures

Outcome measures
Measure	Progression-free Survival Rate/KRAS Negative Group n=5 Participants 200mg TID for treating KRAS negative patients 12 weeks	Progression-free Survival Rate/KRAS Mutant Group n=3 Participants 200mg TID for treating KRAS negative patients 12 weeks	Two Lines Failed Prior Chemotherapies n=7 Participants Patients join with two lines failed prior chemotherapies	More Than Two Lines Failed Prior Chemotherapies n=11 Participants patient failed more than two line chemotherapies before join.
Disease Control Rate (DCR)	40 percentage of participants Interval 5.3 to 85.3	0 percentage of participants Interval 0.0 to 70.8	42.9 percentage of participants Interval 9.9 to 81.6	72.7 percentage of participants Interval 39.0 to 94.0

SECONDARY outcome

Timeframe: 8 hours

PK sampling will be performed on Days 0 and 28 in all patients enrolled in Stage 1.PK endpoints will be derived for intensively sampled PK profiles by T½: terminal half life

Outcome measures

Outcome measures
Measure	Progression-free Survival Rate/KRAS Negative Group n=22 Participants 200mg TID for treating KRAS negative patients 12 weeks	Progression-free Survival Rate/KRAS Mutant Group n=22 Participants 200mg TID for treating KRAS negative patients 12 weeks	Two Lines Failed Prior Chemotherapies Patients join with two lines failed prior chemotherapies	More Than Two Lines Failed Prior Chemotherapies patient failed more than two line chemotherapies before join.
T½: the Time Required for a Quantity to Reduce to Half Its Initial Value	3 hours Interval 0.5 to 4.0	2 hours Interval 0.5 to 4.0	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Population: full sey analysis group

Defined as the proportion of patients whose best overall response is either CR or PR according to RECIST version 1.1. The best overall response is the best response recorded during the first 12 week treatment cycle.

Outcome measures

Outcome measures
Measure	Progression-free Survival Rate/KRAS Negative Group n=26 Participants 200mg TID for treating KRAS negative patients 12 weeks	Progression-free Survival Rate/KRAS Mutant Group 200mg TID for treating KRAS negative patients 12 weeks	Two Lines Failed Prior Chemotherapies Patients join with two lines failed prior chemotherapies	More Than Two Lines Failed Prior Chemotherapies patient failed more than two line chemotherapies before join.
Objective Response Rate (ORR)	0 patients	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: up to week 48

the time from the date of first administration of study drug to death from any cause

Outcome measures

Outcome measures
Measure	Progression-free Survival Rate/KRAS Negative Group n=5 Participants 200mg TID for treating KRAS negative patients 12 weeks	Progression-free Survival Rate/KRAS Mutant Group n=3 Participants 200mg TID for treating KRAS negative patients 12 weeks	Two Lines Failed Prior Chemotherapies n=7 Participants Patients join with two lines failed prior chemotherapies	More Than Two Lines Failed Prior Chemotherapies n=11 Participants patient failed more than two line chemotherapies before join.
Overall Survival week 48	0 percentage of participants Interval 0.0 to 0.0	100 percentage of participants Interval 100.0 to 100.0	28.6 percentage of participants Interval 4.1 to 61.2	39.3 percentage of participants Interval 7.3 to 71.6
Overall Survival week 12	60 percentage of participants Interval 12.6 to 88.2	100 percentage of participants Interval 100.0 to 100.0	100 percentage of participants Interval 100.0 to 100.0	90.9 percentage of participants Interval 50.8 to 98.7

Adverse Events

Antroquinonol (Hocena)

Serious events: 12 serious events

Other events: 31 other events

Deaths: 14 deaths

Serious adverse events

Serious adverse events
Measure	Antroquinonol (Hocena) n=31 participants at risk patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression, unacceptable toxicity, non compliance or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever comes first.
Cardiac disorders Cardiac disorders	6.5% 2/31 • Number of events 3 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Gastrointestinal disorders Gastrointestinal disorders	6.5% 2/31 • Number of events 2 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
General disorders General disorders and administration site conditions	6.5% 2/31 • Number of events 2 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Infections and infestations Infections and infestations	12.9% 4/31 • Number of events 4 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Metabolism and nutrition disorders Metabolism and nutrition disorders	6.5% 2/31 • Number of events 2 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	9.7% 3/31 • Number of events 3 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Nervous system disorders Nervous system disorders	3.2% 1/31 • Number of events 1 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Renal and urinary disorders Renal and urinary disorders	6.5% 2/31 • Number of events 4 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	16.1% 5/31 • Number of events 5 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.

Other adverse events

Other adverse events
Measure	Antroquinonol (Hocena) n=31 participants at risk patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression, unacceptable toxicity, non compliance or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever comes first.
Cardiac disorders Tachycardia	6.5% 2/31 • Number of events 5 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Gastrointestinal disorders Gastrointestinal disorders	96.8% 30/31 • Number of events 30 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
General disorders General disorders and administration site conditions	64.5% 20/31 • Number of events 20 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Infections and infestations Infections and infestations	19.4% 6/31 • Number of events 6 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Investigations Investigations	19.4% 6/31 • Number of events 6 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Metabolism and nutrition disorders Metabolism and nutrition disorders	35.5% 11/31 • Number of events 11 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	25.8% 8/31 • Number of events 8 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	12.9% 4/31 • Number of events 4 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Nervous system disorders Nervous system disorders	35.5% 11/31 • Number of events 11 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Psychiatric disorders Psychiatric disorders	12.9% 4/31 • Number of events 4 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Renal and urinary disorders Renal and urinary disorders	12.9% 4/31 • Number of events 4 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	54.8% 17/31 • Number of events 17 • AEs collected for up to 48 weeks of the study from the time the patient signed the informed consent. Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.

Additional Information

Howard Cheng

Golden Biotechnology Corp.

Phone: +886-2-28086006

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place