Trial Outcomes & Findings for BrUOG 379 Phase Ib/II Trial ONC201 + Nivolumab in MSS mCRC (NCT NCT03791398)

NCT ID: NCT03791398

Last Updated: 2023-02-17

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 13 participants
• Primary outcome timeframe: Cycle 1 (each cycle is approximately 4 weeks) through pre-dosing cycle 2, approximately 1 month
• Results posted on: 2023-02-17

Participant Flow

Participant milestones

Measure	ONC201 Level 1 (Starting Dose Level) 625mg ONC201 Cycle 1 Day -7 dose then once week Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose	ONC201 Level 2 500 mg ONC201 Cycle 1 Day -7 dose then once week Dose level 2 ONC201 500mg: ONC201 500mg + Nivolumab 240mg IV flat dose	ONC201 Level 3 375 mg ONC201 Cycle 1 Day -7 dose then once week Dose level 3 ONC201 375mg: ONC201 375mg + Nivolumab 240mg IV flat dose
Overall Study STARTED	13	0	0
Overall Study COMPLETED	11	0	0
Overall Study NOT COMPLETED	2	0	0

Reasons for withdrawal

Measure	ONC201 Level 1 (Starting Dose Level) 625mg ONC201 Cycle 1 Day -7 dose then once week Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose	ONC201 Level 2 500 mg ONC201 Cycle 1 Day -7 dose then once week Dose level 2 ONC201 500mg: ONC201 500mg + Nivolumab 240mg IV flat dose	ONC201 Level 3 375 mg ONC201 Cycle 1 Day -7 dose then once week Dose level 3 ONC201 375mg: ONC201 375mg + Nivolumab 240mg IV flat dose
Overall Study Progression of Disease Under Study	2	0	0

Baseline Characteristics

BrUOG 379 Phase Ib/II Trial ONC201 + Nivolumab in MSS mCRC

Baseline characteristics by cohort

Measure	ONC201 Level 1 (Starting Dose Level) n=13 Participants 625mg ONC201 Cycle 1 Day -7 dose then once week Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose	ONC201 Level 2 500 mg ONC201 Cycle 1 Day -7 dose then once week Dose level 2 ONC201 500mg: ONC201 500mg + Nivolumab 240mg IV flat dose	ONC201 Level 3 375 mg ONC201 Cycle 1 Day -7 dose then once week Dose level 3 ONC201 375mg: ONC201 375mg + Nivolumab 240mg IV flat dose	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	—	—	8 Participants n=4 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	—	—	5 Participants n=4 Participants
Age, Continuous	60 years n=5 Participants	—	—	60 years n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	—	—	8 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	—	—	5 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	—	—	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	—	—	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	—	—	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	—	—	3 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	—	—	9 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Region of Enrollment United States	13 participants n=5 Participants	—	—	13 participants n=4 Participants

PRIMARY outcome

Timeframe: Cycle 1 (each cycle is approximately 4 weeks) through pre-dosing cycle 2, approximately 1 month

Outcome measures

Measure	ONC201 Level 1 (Starting Dose Level) n=11 Participants 625mg ONC201 Cycle 1 Day -7 dose then once week Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose
Maximum Tolerated Dose of ONC201 With Nivolumab for Phase II	625 mg

PRIMARY outcome

Timeframe: From start of protocol therapy until death or progression, a maximum of 6 months from end of therapy.

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	ONC201 Level 1 (Starting Dose Level) n=11 Participants 625mg ONC201 Cycle 1 Day -7 dose then once week Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose
Progression Free Survival	58 days Interval 9.0 to 97.0

Adverse Events

ONC201 Level 1 (Starting Dose Level)

Serious events: 10 serious events

Other events: 13 other events

Deaths: 11 deaths

Serious adverse events

Measure	ONC201 Level 1 (Starting Dose Level) n=13 participants at risk 625mg ONC201 Cycle 1 Day -7 dose then once week Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose
Gastrointestinal disorders Small intestinal obstruction	30.8% 4/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Investigations Blood bilirubin increased	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Infections and infestations Fungemia	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Gastrointestinal disorders Abdominal pain	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
General disorders Disease progression	61.5% 8/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Renal and urinary disorders Hematuria	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Gastrointestinal disorders Constipation	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Infections and infestations Abdominal infection	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Gastrointestinal disorders Pancreatitis	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Surgical and medical procedures Endoscopic retrograde cholangiopancreatography	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Hepatobiliary disorders Biliary obstruction	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Nervous system disorders Muscle weakness right-sided	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Musculoskeletal and connective tissue disorders Back pain	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Musculoskeletal and connective tissue disorders Neck pain	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Nervous system disorders Dizziness	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.

Other adverse events

Measure	ONC201 Level 1 (Starting Dose Level) n=13 participants at risk 625mg ONC201 Cycle 1 Day -7 dose then once week Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose
Blood and lymphatic system disorders Anemia	15.4% 2/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Metabolism and nutrition disorders Anorexia	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Metabolism and nutrition disorders Dehydration	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Nervous system disorders Dizziness	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Gastrointestinal disorders Dry mouth	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
General disorders Edema limbs	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
General disorders Fatigue	38.5% 5/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Gastrointestinal disorders Gastritis	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Gastrointestinal disorders Abdominal cramping	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Skin and subcutaneous tissue disorders Hyperhidrosis	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Metabolism and nutrition disorders Hyponatremia	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Vascular disorders Hypotension	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Endocrine disorders Hypothyroidism	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Investigations Lipase increased	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Investigations Lymphocyte count decreased	23.1% 3/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Musculoskeletal and connective tissue disorders Myalgia	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	15.4% 2/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Investigations Thyroid stimulating hormone increased	15.4% 2/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Gastrointestinal disorders Vomiting	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.
Investigations Weight loss	7.7% 1/13 • All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.

Additional Information

Brown University Oncology Research Group

BrUOG

Phone: 401-863-3000

Email: BrUOG@Brown.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place