Trial Outcomes & Findings for ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma (NCT NCT03394027)

Last Updated: 2022-08-23

Results Overview

PFS in participants with refractory, metastatic hormone receptor positive breast cancer. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions. And the appearance of one or more new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).

Results posted on

2022-08-23

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) 625mg ONC201 by mouth every 7 days	Cohort 2-Triple Negative Breast Cancer (Male and Female) 625mg ONC201 by mouth every 7 days	Cohort 3-Endometrial Cancer (Female Only) 625mg ONC201 by mouth every 7 days
Overall Study STARTED	10	6	14
Overall Study COMPLETED	7	5	10
Overall Study NOT COMPLETED	3	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) 625mg ONC201 by mouth every 7 days	Cohort 2-Triple Negative Breast Cancer (Male and Female) 625mg ONC201 by mouth every 7 days	Cohort 3-Endometrial Cancer (Female Only) 625mg ONC201 by mouth every 7 days
Overall Study Ineligible	3	1	3
Overall Study Participant declined to participate before treatment started	0	0	1

Baseline Characteristics

ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) n=10 Participants 625mg ONC201 by mouth every 7 days	Cohort 2-Triple Negative Breast Cancer (Male and Female) n=6 Participants 625mg ONC201 by mouth every 7 days	Cohort 3-Endometrial Cancer (Female Only) n=14 Participants 625mg ONC201 by mouth every 7 days	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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	22 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants
Age, Continuous	60.14 years STANDARD_DEVIATION 6.25 • n=5 Participants	53.88 years STANDARD_DEVIATION 8.37 • n=7 Participants	63.65 years STANDARD_DEVIATION 8.99 • n=5 Participants	60.53 years STANDARD_DEVIATION 8.62 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants	30 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants	26 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants	21 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	10 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants	30 participants n=4 Participants

PRIMARY outcome

Timeframe: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).

Population: 7/10 participants were analyzed because 3 participants were ineligible.

Outcome measures

Outcome measures
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) n=7 Participants 625mg ONC201 by mouth every 7 days.	Cohort 1 - Grade 2 Grade 2 is moderate.	Cohort 1 - Grade 3 Grade 3 is severe.	Cohort 1 - Grade 4 Grade 4 is life-threatening.	Cohort 1 - Grade 5 Grade 5 is death related to adverse event.	Cohort 2 - Grade 1 Grade 1 is mild.	Cohort 2 - Grade 2 Grade 2 is moderate.	Cohort 2 - Grade 3 Grade 3 is severe.	Cohort 2 - Grade 4 Grade 4 is life-threatening.	Cohort 2 - Grade 5 Grade 5 is death related to adverse event.	Cohort 3 - Grade 1 Grade 1 is mild.	Cohort 3 - Grade 2 Grade 2 is moderate.	Cohort 3 - Grade 3 Grade 3 is severe.	Cohort 3 - Grade 4 Grade 4 is life-threatening.	Cohort 3 - Grade 5 Grade 5 is death related to adverse event.
Cohort 1 - Progression-free Survival (PFS)	1.9 Months Interval 0.6 to 4.0	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).

Population: 5/6 participants were analyzed because 1 participant was ineligible.

Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with metastatic triple negative breast cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.

Outcome measures

Outcome measures
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) n=5 Participants 625mg ONC201 by mouth every 7 days.	Cohort 1 - Grade 2 Grade 2 is moderate.	Cohort 1 - Grade 3 Grade 3 is severe.	Cohort 1 - Grade 4 Grade 4 is life-threatening.	Cohort 1 - Grade 5 Grade 5 is death related to adverse event.	Cohort 2 - Grade 1 Grade 1 is mild.	Cohort 2 - Grade 2 Grade 2 is moderate.	Cohort 2 - Grade 3 Grade 3 is severe.	Cohort 2 - Grade 4 Grade 4 is life-threatening.	Cohort 2 - Grade 5 Grade 5 is death related to adverse event.	Cohort 3 - Grade 1 Grade 1 is mild.	Cohort 3 - Grade 2 Grade 2 is moderate.	Cohort 3 - Grade 3 Grade 3 is severe.	Cohort 3 - Grade 4 Grade 4 is life-threatening.	Cohort 3 - Grade 5 Grade 5 is death related to adverse event.
Cohort 2 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST) Complete Response	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Cohort 2 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST) Partial Response	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).

Population: 10/14 participants were analyzed because 3 participants were ineligible, and 1 participant declined to participate before treatment started.

Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with advanced or metastatic endometrial cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.

Outcome measures

Outcome measures
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) n=10 Participants 625mg ONC201 by mouth every 7 days.	Cohort 1 - Grade 2 Grade 2 is moderate.	Cohort 1 - Grade 3 Grade 3 is severe.	Cohort 1 - Grade 4 Grade 4 is life-threatening.	Cohort 1 - Grade 5 Grade 5 is death related to adverse event.	Cohort 2 - Grade 1 Grade 1 is mild.	Cohort 2 - Grade 2 Grade 2 is moderate.	Cohort 2 - Grade 3 Grade 3 is severe.	Cohort 2 - Grade 4 Grade 4 is life-threatening.	Cohort 2 - Grade 5 Grade 5 is death related to adverse event.	Cohort 3 - Grade 1 Grade 1 is mild.	Cohort 3 - Grade 2 Grade 2 is moderate.	Cohort 3 - Grade 3 Grade 3 is severe.	Cohort 3 - Grade 4 Grade 4 is life-threatening.	Cohort 3 - Grade 5 Grade 5 is death related to adverse event.
Cohort 3 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST) Complete Response	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Cohort 3 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST) Partial Response	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 13 months and 28 days for cohort 1, 11 months and 12 days for cohort 2, and 34 months and 29 days for cohort 3.

Population: 7/10 participants were analyzed in cohort 1 because 3 participants were ineligible. 5/6 participants were analyzed in cohort 2 because 1 participant was ineligible. And 10/14 participants were analyzed in cohort 3 because 3 participants were ineligible, and 1 participant declined to participate before treatment started. Serious adverse events are denoted by an \*.

Serious and non-serious adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, , Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Outcome measures

Outcome measures
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) n=7 Participants 625mg ONC201 by mouth every 7 days.	Cohort 1 - Grade 2 n=7 Participants Grade 2 is moderate.	Cohort 1 - Grade 3 n=7 Participants Grade 3 is severe.	Cohort 1 - Grade 4 n=7 Participants Grade 4 is life-threatening.	Cohort 1 - Grade 5 n=7 Participants Grade 5 is death related to adverse event.	Cohort 2 - Grade 1 n=5 Participants Grade 1 is mild.	Cohort 2 - Grade 2 n=5 Participants Grade 2 is moderate.	Cohort 2 - Grade 3 n=5 Participants Grade 3 is severe.	Cohort 2 - Grade 4 n=5 Participants Grade 4 is life-threatening.	Cohort 2 - Grade 5 n=5 Participants Grade 5 is death related to adverse event.	Cohort 3 - Grade 1 n=10 Participants Grade 1 is mild.	Cohort 3 - Grade 2 n=10 Participants Grade 2 is moderate.	Cohort 3 - Grade 3 n=10 Participants Grade 3 is severe.	Cohort 3 - Grade 4 n=10 Participants Grade 4 is life-threatening.	Cohort 3 - Grade 5 n=10 Participants Grade 5 is death related to adverse event.
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Vomiting	3 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Memory impairment	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Vaginal discharge	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Anemia	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Abdominal distension	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Abdominal pain	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Abdominal pain	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Alanine aminotransferase increased	2 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Alkaline phosphatase increased	0 Adverse events	2 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Anemia	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	5 Adverse events	3 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Anorexia	4 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Arthralgia	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Ascites	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Aspartate aminotransferase increased	0 Adverse events	1 Adverse events	3 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	3 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Back pain	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Blood bilirubin increased	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Breast pain	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Confusion	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Constipation	0 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Cough	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Creatinine increased	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Dehydration	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Dizziness	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	5 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Dysarthria	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Dysgeusia	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Dyspepsia	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Dyspnea	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Edema limbs	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Epistaxis	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Facial pain	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Fall	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Fall	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Fatigue	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Flu like symptoms	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Flushing	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Gastroesophageal reflux disease	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Headache	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Hyperhidrosis	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Hypermagnesemia	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Hypoalbuminemia	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Hypocalcemia	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Hypomagnesemia	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Hypotension	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Insomnia	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Lethargy	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Lymphedema	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Lymphocyte count decreased	2 Adverse events	2 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events	2 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Malaise	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Mucosal infection	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Myalgia	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Nervous system disorders - Other, specify	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Non-cardiac chest pain	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Pain	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Pain	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Pain in extremity	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Paresthesia	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Pleural effusion	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Pleural effusion	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Proteinuria	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Stroke	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Thromboembolic event	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Transient ischemic attacks	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Tremor	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Upper respiratory infection	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Urinary tract infection	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Urinary tract infection	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Vaginal hemorrhage	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Vascular access complication	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Vomiting	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Weight loss	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Wheezing	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 White blood cell decreased	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Diarrhea	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Sepsis	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Atrial flutter	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Breast pain	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Cardiac arrest	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Dehydration	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Diarrhea	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Dyspnea	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Fatigue	2 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	5 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Fever	3 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Fever	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Hot flashes	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Hypophosphatemia	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Laryngeal hemorrhage	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Nausea	3 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Nausea	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Sinus tachycardia	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Sinus tachycardia	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Rhinorrhea	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Peripheral sensory neuropathy	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Platelet count decreased	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Tumor hemorrhage	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 *Pneumonitis	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Pruritus	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 Rash maculo-papular	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events

SECONDARY outcome

Timeframe: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).

Population: 7/10 participants were analyzed because 3 participants were ineligible.

Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with refractory, metastatic hormone receptor positive breast cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.

Outcome measures

Outcome measures
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) n=7 Participants 625mg ONC201 by mouth every 7 days.	Cohort 1 - Grade 2 Grade 2 is moderate.	Cohort 1 - Grade 3 Grade 3 is severe.	Cohort 1 - Grade 4 Grade 4 is life-threatening.	Cohort 1 - Grade 5 Grade 5 is death related to adverse event.	Cohort 2 - Grade 1 Grade 1 is mild.	Cohort 2 - Grade 2 Grade 2 is moderate.	Cohort 2 - Grade 3 Grade 3 is severe.	Cohort 2 - Grade 4 Grade 4 is life-threatening.	Cohort 2 - Grade 5 Grade 5 is death related to adverse event.	Cohort 3 - Grade 1 Grade 1 is mild.	Cohort 3 - Grade 2 Grade 2 is moderate.	Cohort 3 - Grade 3 Grade 3 is severe.	Cohort 3 - Grade 4 Grade 4 is life-threatening.	Cohort 3 - Grade 5 Grade 5 is death related to adverse event.
Cohort 1 - Overall Response Rate (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST) Partial Response	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Cohort 1 - Overall Response Rate (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST) Complete Response	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).

Clinical benefit is Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (i.e., at least a 20% increase in the sum of the diameters of target lesions).

Outcome measures

Outcome measures
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) n=7 Participants 625mg ONC201 by mouth every 7 days.	Cohort 1 - Grade 2 n=5 Participants Grade 2 is moderate.	Cohort 1 - Grade 3 n=10 Participants Grade 3 is severe.	Cohort 1 - Grade 4 Grade 4 is life-threatening.	Cohort 1 - Grade 5 Grade 5 is death related to adverse event.	Cohort 2 - Grade 1 Grade 1 is mild.	Cohort 2 - Grade 2 Grade 2 is moderate.	Cohort 2 - Grade 3 Grade 3 is severe.	Cohort 2 - Grade 4 Grade 4 is life-threatening.	Cohort 2 - Grade 5 Grade 5 is death related to adverse event.	Cohort 3 - Grade 1 Grade 1 is mild.	Cohort 3 - Grade 2 Grade 2 is moderate.	Cohort 3 - Grade 3 Grade 3 is severe.	Cohort 3 - Grade 4 Grade 4 is life-threatening.	Cohort 3 - Grade 5 Grade 5 is death related to adverse event.
Number of Participants in Cohorts 1, 2, and 3 With Clinical Benefit Stable Disease	1 Participants	1 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—	—	—
Number of Participants in Cohorts 1, 2, and 3 With Clinical Benefit Complete Response	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—
Number of Participants in Cohorts 1, 2, and 3 With Clinical Benefit Partial Response	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Every 8 weeks, while on treatment, up to 3 months

Population: 5/6 participants were analyzed in cohort 2 because 1 participant was ineligible. And 10/14 participants were analyzed in cohort 3 because 3 participants were ineligible, and 1 participant declined to participate before treatment started.

PFS in participants with triple negative breast cancer and endometrial cancer. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions. And the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) n=5 Participants 625mg ONC201 by mouth every 7 days.	Cohort 1 - Grade 2 n=10 Participants Grade 2 is moderate.	Cohort 1 - Grade 3 Grade 3 is severe.	Cohort 1 - Grade 4 Grade 4 is life-threatening.	Cohort 1 - Grade 5 Grade 5 is death related to adverse event.	Cohort 2 - Grade 1 Grade 1 is mild.	Cohort 2 - Grade 2 Grade 2 is moderate.	Cohort 2 - Grade 3 Grade 3 is severe.	Cohort 2 - Grade 4 Grade 4 is life-threatening.	Cohort 2 - Grade 5 Grade 5 is death related to adverse event.	Cohort 3 - Grade 1 Grade 1 is mild.	Cohort 3 - Grade 2 Grade 2 is moderate.	Cohort 3 - Grade 3 Grade 3 is severe.	Cohort 3 - Grade 4 Grade 4 is life-threatening.	Cohort 3 - Grade 5 Grade 5 is death related to adverse event.
Cohorts 2 and 3 - Progression-free Survival (PFS)	1.2 Months Interval 0.5 to 1.8	2 Months Interval 0.6 to 3.0	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 13 months and 28 days for cohort 1, 11 months and 12 days for cohort 2, and 34 months and 29 days for cohort 3.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female) n=7 Participants 625mg ONC201 by mouth every 7 days.	Cohort 1 - Grade 2 n=5 Participants Grade 2 is moderate.	Cohort 1 - Grade 3 n=10 Participants Grade 3 is severe.	Cohort 1 - Grade 4 Grade 4 is life-threatening.	Cohort 1 - Grade 5 Grade 5 is death related to adverse event.	Cohort 2 - Grade 1 Grade 1 is mild.	Cohort 2 - Grade 2 Grade 2 is moderate.	Cohort 2 - Grade 3 Grade 3 is severe.	Cohort 2 - Grade 4 Grade 4 is life-threatening.	Cohort 2 - Grade 5 Grade 5 is death related to adverse event.	Cohort 3 - Grade 1 Grade 1 is mild.	Cohort 3 - Grade 2 Grade 2 is moderate.	Cohort 3 - Grade 3 Grade 3 is severe.	Cohort 3 - Grade 4 Grade 4 is life-threatening.	Cohort 3 - Grade 5 Grade 5 is death related to adverse event.
Here is the Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).	7 Participants	5 Participants	10 Participants	—	—	—	—	—	—	—	—	—	—	—	—

Adverse Events

Cohort 1-Hormone Receptor (HR) + Breast Cancer (Male and Female)

Serious events: 4 serious events

Other events: 7 other events

Deaths: 2 deaths

Cohort 2-Triple Negative Breast Cancer (Male and Female)

Serious events: 3 serious events

Other events: 5 other events

Deaths: 1 deaths

Cohort 3-Endometrial Cancer (Female Only)

Serious events: 5 serious events

Other events: 10 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Stanley Lipkowitz

National Cancer Institute

Phone: 240-760-6129

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place