Trial Outcomes & Findings for A Study of VAL401 in the Treatment of Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NCT NCT02875340)

Last Updated: 2018-10-15

Results Overview

PFS is defined as the time from screening to disease progression (or death if the patient died before progression), with progression date nominally defined as the date the patient was withdrawn from the trial, where the Principal Investigator has determined by their professional discretion the patient has symptomatic disease progression.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

6 months

Results posted on

2018-10-15

Participant Flow

Recruitment period: 31 October 2016 - 19 June 2017

Participant milestones

Participant milestones
Measure	VAL401 Treatment Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg)
Overall Study STARTED	8
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	VAL401 Treatment Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg)
Overall Study Death	2
Overall Study Withdrawal by Subject	2
Overall Study Physician Decision	3
Overall Study Adverse Event	1

Baseline Characteristics

A Study of VAL401 in the Treatment of Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VAL401 Treatment n=8 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg)
Age, Continuous	65.8 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Georgia	8 participants n=5 Participants
Smokers Smokers	0 Participants n=5 Participants
Smokers Ex-smokers	4 Participants n=5 Participants
Smokers Never-smokers	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	VAL401 Treatment - Intention to Treat Group n=7 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This group includes all patients who completed screening, but excludes the one patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Per Protocol Group n=5 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This groups excludes the 2 patients received treatment for less than 10 days, as well as the patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Day 15 (6 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 6 mg daily dose level	VAL401 Treatment - Day 15 (8 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 8 mg daily dose level
Progression-free Survival (PFS)	5.2 weeks Interval 0.4 to 11.6	7.2 weeks Interval 4.0 to 11.6	—	—

SECONDARY outcome

Timeframe: 6 months

Population: Each question is scored on a scale of 1 to 4, with each patient assessed for improvement or deterioration of Quality of Life for each life category stated. The number of patients, improving, deteriorating or remaining stable for each measure is reported out of the total of 8 patients assessed.

Changes in patient quality of life measured by EORTC Health-related Quality of Life (HRQoL) assessment questionnaire QLQ-C30 (Cancer specific questionnaire).

Outcome measures

Outcome measures
Measure	VAL401 Treatment - Intention to Treat Group n=8 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This group includes all patients who completed screening, but excludes the one patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Per Protocol Group Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This groups excludes the 2 patients received treatment for less than 10 days, as well as the patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Day 15 (6 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 6 mg daily dose level	VAL401 Treatment - Day 15 (8 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 8 mg daily dose level
Patient Quality of Life During VAL401 Treatment Improvement in diarrhoea · Status improved	1 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment ECOG data · Not measured	4 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment ECOG data · Status maintained	3 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment ECOG data · Status deteriorated	1 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment ECOG data · Status improved	0 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in pain · Not measured	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in pain · Status maintained	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in pain · Status deteriorated	0 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in pain · Status improved	4 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in Insomnia · Not measured	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in Insomnia · Status maintained	3 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in Insomnia · Status deteriorated	1 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in Insomnia · Status improved	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in lack of appetite · Not measured	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in lack of appetite · Status maintained	3 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in lack of appetite · Status deteriorated	1 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in lack of appetite · Status improved	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in nausea/vomiting · Not measured	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in nausea/vomiting · Status maintained	4 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in nausea/vomiting · Status deteriorated	0 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in nausea/vomiting · Status improved	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in fatigue · Not measured	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in fatigue · Status maintained	1 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in fatigue · Status deteriorated	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in fatigue · Status improved	3 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in irritability · Not measured	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in irritability · Status maintained	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in irritability · Status deteriorated	3 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in irritability · Status improved	1 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in depression · Not measured	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in depression · Status maintained	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in depression · Status deteriorated	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in depression · Status improved	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in anxiety · Not measured	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in anxiety · Status maintained	1 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in anxiety · Status deteriorated	3 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in anxiety · Status improved	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in diarrhoea · Not measured	2 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in diarrhoea · Status maintained	4 Participants	—	—	—
Patient Quality of Life During VAL401 Treatment Improvement in diarrhoea · Status deteriorated	1 Participants	—	—	—

SECONDARY outcome

Timeframe: 6 months

Population: Total number of patients reporting Adverse Events or Serious Adverse Events (excluding death)

Ongoing evaluation of Adverse Events during treatment with VAL401. Events assessed for number of patients affected, severity of event, likelihood of event being related to the drug treatment and whether the event is an expected/known side effect of Risperidone.

Outcome measures

Outcome measures
Measure	VAL401 Treatment - Intention to Treat Group n=8 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This group includes all patients who completed screening, but excludes the one patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Per Protocol Group Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This groups excludes the 2 patients received treatment for less than 10 days, as well as the patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Day 15 (6 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 6 mg daily dose level	VAL401 Treatment - Day 15 (8 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 8 mg daily dose level
Number of Participants Reporting Adverse Events and Serious Adverse Events Adverse Events reported · Number participants reporting events	8 Participants	—	—	—
Number of Participants Reporting Adverse Events and Serious Adverse Events Adverse Events reported · Number participants reporting no events	0 Participants	—	—	—
Number of Participants Reporting Adverse Events and Serious Adverse Events Serious Adverse Events Reported · Number participants reporting events	1 Participants	—	—	—
Number of Participants Reporting Adverse Events and Serious Adverse Events Serious Adverse Events Reported · Number participants reporting no events	7 Participants	—	—	—

SECONDARY outcome

Timeframe: 6 months

Population: Participants scheduled to receive scans at screening, 3 months and 6 months. 2 participants attended CT scans at 3 months, or at their final visit (if earlier).

Objective tumour response rates according to RECIST 1.1 for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Outcome measures

Outcome measures
Measure	VAL401 Treatment - Intention to Treat Group n=2 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This group includes all patients who completed screening, but excludes the one patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Per Protocol Group Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This groups excludes the 2 patients received treatment for less than 10 days, as well as the patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Day 15 (6 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 6 mg daily dose level	VAL401 Treatment - Day 15 (8 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 8 mg daily dose level
Number of Patients With Disease Control Participants receiving mid-treatment CT scan	2 Participants	—	—	—
Number of Patients With Disease Control Primary target tumour increased by 10% or less	2 Participants	—	—	—
Number of Patients With Disease Control Participants demonstrating Complete Response	0 Participants	—	—	—
Number of Patients With Disease Control Participants demonstrating Partial Response	0 Participants	—	—	—
Number of Patients With Disease Control Participants demonstrating Progressive disease	0 Participants	—	—	—
Number of Patients With Disease Control Participants demonstrating Stable Disease	2 Participants	—	—	—

SECONDARY outcome

Timeframe: 1 Day and 2 weeks

Population: Pharmacokinetic measurements include total of Risperidone plus metabolite 9-hydroxy-Risperidone as "total actives" Note: 3 out of 8 patients completed PK analysis at Day 15, the remaining 5 patients did not undergo Day 15 PK analysis due to protocol deviations or early withdrawal from the trial.

Assessment of Cmax in collected blood samples on Day 1 and Day 15 of Cycle 1, collected at time points: pre-dose (0h) then 10, 15, 30 minutes, 1, 2, 4, 8, 10 and 24 hours after administration of VAL401.

Outcome measures

Outcome measures
Measure	VAL401 Treatment - Intention to Treat Group n=8 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This group includes all patients who completed screening, but excludes the one patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Per Protocol Group n=1 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This groups excludes the 2 patients received treatment for less than 10 days, as well as the patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Day 15 (6 mg) n=1 Participants Pharmacokinetic measurements taken on Day 15 of dosing on 6 mg daily dose level	VAL401 Treatment - Day 15 (8 mg) n=1 Participants Pharmacokinetic measurements taken on Day 15 of dosing on 8 mg daily dose level
Peak Plasma Concentration (Cmax)	30.5 ng/mL Interval 13.0 to 65.0	20 ng/mL Interval 20.0 to 20.0	102 ng/mL Interval 102.0 to 102.0	464 ng/mL Interval 464.0 to 464.0

SECONDARY outcome

Timeframe: 1 Day and 2 weeks

Population: Pharmacokinetic measurements include total of Risperidone plus metabolite 9-hydroxy-Risperidone as "total actives". Note: 3 out of 8 patients completed PK analysis at Day 15, the remaining 5 patients did not undergo Day 15 PK analysis due to protocol deviations or early withdrawal from the trial.

Assessment of trough plasma concentration (Cmin) in collected blood samples on Day 1 and Day 15 of Cycle 1, collected at time points: pre-dose (0h) then 10, 15, 30 minutes, 1, 2, 4, 8, 10 and 24 hours after administration of VAL401.

Outcome measures

Outcome measures
Measure	VAL401 Treatment - Intention to Treat Group n=8 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This group includes all patients who completed screening, but excludes the one patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Per Protocol Group n=1 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This groups excludes the 2 patients received treatment for less than 10 days, as well as the patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Day 15 (6 mg) n=1 Participants Pharmacokinetic measurements taken on Day 15 of dosing on 6 mg daily dose level	VAL401 Treatment - Day 15 (8 mg) n=1 Participants Pharmacokinetic measurements taken on Day 15 of dosing on 8 mg daily dose level
Trough Plasma Concentration (Cmin)	10.125 ng/mL Interval 4.0 to 26.0	11 ng/mL Interval 11.0 to 11.0	35 ng/mL Interval 35.0 to 35.0	111 ng/mL Interval 111.0 to 111.0

SECONDARY outcome

Timeframe: 1 Day and 2 weeks

Assessment of plasma half-life of VAL401 (t 1/2) in collected blood samples on Day 1 and Day 15 of Cycle 1, collected at time points: pre-dose (0h) then 10, 15, 30 minutes, 1, 2, 4, 8, 10 and 24 hours after administration of VAL401.

Outcome measures

Outcome measures
Measure	VAL401 Treatment - Intention to Treat Group n=8 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This group includes all patients who completed screening, but excludes the one patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Per Protocol Group n=1 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This groups excludes the 2 patients received treatment for less than 10 days, as well as the patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Day 15 (6 mg) n=1 Participants Pharmacokinetic measurements taken on Day 15 of dosing on 6 mg daily dose level	VAL401 Treatment - Day 15 (8 mg) n=1 Participants Pharmacokinetic measurements taken on Day 15 of dosing on 8 mg daily dose level
Plasma VAL401 Half-life (t 1/2)	9 hours Interval 7.0 to 36.0	26 hours Interval 26.0 to 26.0	30 hours Interval 30.0 to 30.0	16 hours Interval 16.0 to 16.0

SECONDARY outcome

Timeframe: 6 months

Defined as the time from screening to death if the patient dies within the period that the site is open

Outcome measures

Outcome measures
Measure	VAL401 Treatment - Intention to Treat Group n=7 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This group includes all patients who completed screening, but excludes the one patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Per Protocol Group n=5 Participants Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg). This groups excludes the 2 patients received treatment for less than 10 days, as well as the patient for whom the date of diagnosis is inconsistent.	VAL401 Treatment - Day 15 (6 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 6 mg daily dose level	VAL401 Treatment - Day 15 (8 mg) Pharmacokinetic measurements taken on Day 15 of dosing on 8 mg daily dose level
Overall Survival	7.8 weeks Interval 0.4 to 15.3	10.9 weeks Interval 6.9 to 15.3	—	—

Adverse Events

VAL401 Treatment

Serious events: 1 serious events

Other events: 8 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	VAL401 Treatment n=8 participants at risk Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg)
Blood and lymphatic system disorders Anaemia	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)

Other adverse events

Other adverse events
Measure	VAL401 Treatment n=8 participants at risk Patients received VAL401 oral formulation once daily according to their level of tolerance (2 mg - 10 mg)
Social circumstances Fatigue	75.0% 6/8 • Number of events 9 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Nervous system disorders Vertigo	37.5% 3/8 • Number of events 3 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Respiratory, thoracic and mediastinal disorders Dyspnea	25.0% 2/8 • Number of events 2 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Social circumstances Sleepiness	25.0% 2/8 • Number of events 6 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Nervous system disorders Nervousness	25.0% 2/8 • Number of events 2 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Nervous system disorders Excitement	25.0% 2/8 • Number of events 2 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Nervous system disorders Agression	25.0% 2/8 • Number of events 2 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Cardiac disorders Atrial fibrillation	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Cardiac disorders Bifasicular block	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Cardiac disorders Supraventricular extrasystole	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Cardiac disorders Ventricular extrasystole	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Cardiac disorders Ventricular tachycardia	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Blood and lymphatic system disorders Anaemia	12.5% 1/8 • Number of events 5 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Vascular disorders Peripheral venous thrombosis	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Metabolism and nutrition disorders Hypoalbuminemia	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Metabolism and nutrition disorders Hyponatremia	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Cardiac disorders Chest pain	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Vascular disorders Pericardial effusion	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Vascular disorders Pleural effusion	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Musculoskeletal and connective tissue disorders Arthalgia	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Musculoskeletal and connective tissue disorders Back Pain	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Hepatobiliary disorders ALP rise	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)
Vascular disorders Left lower extremity edema	12.5% 1/8 • Number of events 1 • Adverse Event data collected from time of screening until patient final visit (up to 6 months)

Additional Information

Suzanne Dilly

ValiSeek Limited

Phone: +442030084416

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place