Trial Outcomes & Findings for ONC201 With a Methionine-Restricted Diet in Patients With Metastatic Triple Negative Breast Cancer (NCT NCT03733119)

Last Updated: 2022-03-10

Results Overview

ORR will be estimated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, by dividing the total number of responders (complete plus partial responses plus CR or PR) or (CR or PR), respectively, by number of subjects with measurable disease and the exact 95% confidence interval will be provided. Due to early termination with few participants, only the counts of events have been reported.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

maximum follow up time was 1 year

Results posted on

2022-03-10

Participant Flow

4 participants enrolled, 1 determined not to meet the eligibility criteria, 3 participants started treatment

Participant milestones

Participant milestones
Measure	Akt/ERK Inhibitor ONC201 Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	2	2
Overall Study Treated	2	1
Overall Study Stopped Treatment After 1 Dose	1	0
Overall Study Stopped Treatment After 3 Cycles	1	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Akt/ERK Inhibitor ONC201 Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study Physician Decision	2	1
Overall Study ineligible to treat per protocol	0	1

Baseline Characteristics

ONC201 With a Methionine-Restricted Diet in Patients With Metastatic Triple Negative Breast Cancer

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: maximum follow up time was 1 year

Population: study was terminated early, data for response rate at 2 years per protocol was not collected

Outcome measures

Outcome measures
Measure	Akt/ERK Inhibitor ONC201 n=2 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet n=1 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Response Rate (ORR) - Number of Participants Who Responded to Treatment	0 Participants	0 Participants

SECONDARY outcome

Timeframe: maximum follow up time was 1 year

Population: study was terminated early, data for progression free survival at 2 years not collected

Will be summarized using Kaplan-Meier estimates of the median survival times. Point estimates as well as 95% confidence intervals will be provided. Due to early termination with few participants, only the counts of events have been reported.

Outcome measures

Outcome measures
Measure	Akt/ERK Inhibitor ONC201 n=2 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet n=1 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS) - Number of Participants With PFS	0 Participants	0 Participants

SECONDARY outcome

Timeframe: maximum follow up time was 1 year

Population: study was terminated early, data for overall survival at 2 years not collected

Outcome measures

Outcome measures
Measure	Akt/ERK Inhibitor ONC201 n=2 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet n=1 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS) - Number of Participants Who Survived the Study Period	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At 4 months

CBR will be estimated according to RECIST 1.1, by dividing the total number of responders (complete plus partial responses plus CR or PR or stable disease \[SD\]), by number of subjects with measurable disease and the exact 95% confidence interval will be provided. Due to early termination with few participants, only the counts of events have been reported.

Outcome measures

Outcome measures
Measure	Akt/ERK Inhibitor ONC201 n=2 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet n=1 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Clinical Benefit Rate (CBR) - Number of Participants Who Experienced Clinical Benefit	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: duration of response could not be calculated as there were no responders on study

Will be measured using Kaplan-Meier methodology. A 95% confidence interval will be provided for the median duration of response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 30 days after last dose of study drug, up to 4 months on study

Population: See Adverse Events Module for a complete summary of adverse events data.

Incidence of adverse events as measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Safety and tolerability will be assessed by frequency tables. Also, metabolic indices in patients with metastatic triple negative breast cancer (TNBC) treated with ONC-201 and a methionine-restricted diet will be assessed by frequency tables and descriptive statistics.

Outcome measures

Outcome measures
Measure	Akt/ERK Inhibitor ONC201 n=2 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet n=1 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Incidence of Adverse Events - Number of Participants Who Experienced Adverse Events	2 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 2 years

Population: study was terminated early, data for outcome at 2 years not collected, see Number of Participants with Development or Worsening of Brain Metastases Outcome for more information

Will be summarized using Kaplan-Meier methodology.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 4 months

Population: one participant was determined to have a brain metastasis prior to treatment, outcome measure added to provide additional information about participant population

Outcome measures

Outcome measures
Measure	Akt/ERK Inhibitor ONC201 n=1 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet n=1 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Participants With Developing or Worsening Brain Metastasis	0 Participants	0 Participants

Adverse Events

Akt/ERK Inhibitor ONC201

Serious events: 1 serious events

Other events: 2 other events

Deaths: 2 deaths

Akt/ERK Inhibitor ONC201, Methionine-restricted Diet

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Akt/ERK Inhibitor ONC201 n=2 participants at risk Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet n=1 participants at risk Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cardiac disorders Pericardial tamponade	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Cardiac disorders Pericardial effusion	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Infections and infestations Lung infection	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Nervous system disorders Intracranial hemorrhage	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug

Other adverse events

Additional Information

Kari Wisinski, MD

University of Wisconsin Carbone Cancer Center

Phone: 608-262-2876

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Akt/ERK Inhibitor ONC201 n=2 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet n=2 Participants Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total n=4 Participants Total of all reporting groups
Age, Customized Age (years) · 20-29	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Customized Age (years) · 30-39	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized Age (years) · 40-49	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Customized Age (years) · 50-59	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Customized Age (years) · 60-69	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants

Measure	Akt/ERK Inhibitor ONC201 n=2 participants at risk Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet n=1 participants at risk Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug
Metabolism and nutrition disorders Anorexia	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Investigations Aspartate aminotransferase increased	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Investigations Blood bilirubin increased	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Eye disorders Blurred vision	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Injury, poisoning and procedural complications Bruising	0.00% 0/2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Gastrointestinal disorders Constipation	0.00% 0/2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Psychiatric disorders Depression	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Gastrointestinal disorders Diarrhea	50.0% 1/2 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Nervous system disorders Dizziness	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Reproductive system and breast disorders Dyspnea	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Blood and lymphatic system disorders Eosinophilia	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
General disorders Fatigue	100.0% 2/2 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
General disorders Fever	50.0% 1/2 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Nervous system disorders Headache	100.0% 2/2 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Renal and urinary disorders Hemoglobinuria	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Metabolism and nutrition disorders Hyperglycemia	100.0% 2/2 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Metabolism and nutrition disorders Hypernatremia	0.00% 0/2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 2/2 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Metabolism and nutrition disorders Hyponatremia	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Psychiatric disorders Insomnia	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Psychiatric disorders Irritability	50.0% 1/2 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Investigations Lymphocyte count decreased	50.0% 1/2 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Gastrointestinal disorders Nausea	100.0% 2/2 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
General disorders Non-cardiac chest pain	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Infections and infestations Otitis media	0.00% 0/2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
General disorders Pain	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug
Renal and urinary disorders Proteinuria	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Infections and infestations Sinusitis	0.00% 0/2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Infections and infestations Urinary tract infection	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Eye disorders Vision decreased	50.0% 1/2 • Number of events 1 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Gastrointestinal disorders Vomiting	100.0% 2/2 • Number of events 4 • up to 4 months Participants were followed for 30 days after last dose of study drug	0.00% 0/1 • up to 4 months Participants were followed for 30 days after last dose of study drug
Investigations White blood cell decreased	0.00% 0/2 • up to 4 months Participants were followed for 30 days after last dose of study drug	100.0% 1/1 • Number of events 2 • up to 4 months Participants were followed for 30 days after last dose of study drug