Trial Outcomes & Findings for Phase 1/2 Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies (NCT NCT04383938)

Last Updated: 2025-05-13

Results Overview

To determine the Frequency of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) related to APR-246 in combination with pembrolizumab.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Through study completion, approximately 1 year

Results posted on

2025-05-13

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental: Safety Lead In Patients with advanced solid tumors. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 1 Patients with advanced gastric cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 2 Patients with advanced urothelial/bladder cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 3 Patients with advanced NSCLC. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle
Overall Study STARTED	6	8	5	21
Overall Study COMPLETED	6	6	5	20
Overall Study NOT COMPLETED	0	2	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 1/2 Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: Safety Lead In n=6 Participants Patients with advanced solid tumors. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 1 Patients With Advanced Gastric Cancer. n=8 Participants Patients with advanced gastric cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 2 n=5 Participants Patients with advanced urothelial/bladder cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 3 Patients With Advanced NSCLC n=21 Participants Patients with advanced NSCLC. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Total n=40 Participants Total of all reporting groups
Age, Continuous	58 years n=5 Participants	67 years n=7 Participants	67 years n=5 Participants	67 years n=4 Participants	66 years n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	13 Participants n=4 Participants	17 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants	23 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	16 Participants n=4 Participants	31 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Region of Enrollment United States	6 participants n=5 Participants	8 participants n=7 Participants	5 participants n=5 Participants	21 participants n=4 Participants	40 participants n=21 Participants

PRIMARY outcome

Timeframe: Through study completion, approximately 1 year

Population: Data is presented by cohort/arm. 3 out of the 40 overall patients did not receive treatment on study. 37 total patients were analyzed

To determine the Frequency of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) related to APR-246 in combination with pembrolizumab.

Outcome measures

Outcome measures
Measure	Experimental: Safety Lead In n=6 Participants Patients with advanced solid tumors. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 1 n=6 Participants Patients with advanced gastric cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 2 n=5 Participants Patients with advanced urothelial/bladder cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 3 n=20 Participants Patients with advanced NSCLC. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle
To Evaluate the Safety of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumors.	6 participants	6 participants	5 participants	20 participants

PRIMARY outcome

Timeframe: Through safety lead in period, during cycle 1 (approximately 21 days)

Population: Experimental: Safety Lead In" Arm/Group was analyzed for this Outcome Measure

To determine the dose of APR-246 to be selected for the expansion phase based on the occurence of dose limiting toxicities (DLTs) experienced during the safety assessment period

Outcome measures

Outcome measures
Measure	Experimental: Safety Lead In n=6 Participants Patients with advanced solid tumors. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 1 Patients with advanced gastric cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 2 Patients with advanced urothelial/bladder cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 3 Patients with advanced NSCLC. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle
To Confirm the Recommended Phase 2 Dose (RP2D) for APR-246 in Combination With Pembrolizumab	4.5 g/d	—	—	—

Adverse Events

Experimental: Safety Lead In

Serious events: 1 serious events

Other events: 6 other events

Deaths: 5 deaths

Experimental: Expansion 1

Serious events: 4 serious events

Other events: 5 other events

Deaths: 4 deaths

Experimental: Expansion 2

Serious events: 3 serious events

Other events: 5 other events

Deaths: 2 deaths

Experimental: Expansion 3

Serious events: 7 serious events

Other events: 20 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Medical Advisor

Aprea Therapeutics

Phone: 215-948-4119

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Experimental: Safety Lead In n=6 participants at risk Patients with advanced solid tumors. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 1 n=6 participants at risk Patients with advanced gastric cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 2 n=5 participants at risk Patients with advanced urothelial/bladder cancer. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle	Experimental: Expansion 3 n=20 participants at risk Patients with advanced NSCLC. APR 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	15.0% 3/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	10.0% 2/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
General disorders Disease Progression	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
General disorders Pain	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	20.0% 1/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
General disorders Asthenia	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
General disorders Pyrexia	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Gastrointestinal disorders Abdominal Pain	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	20.0% 1/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	20.0% 1/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Gastrointestinal disorders Abdominal Pain upper	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Gastrointestinal disorders Nausea	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	20.0% 1/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Vascular disorders Hypotension	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	20.0% 1/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Vascular disorders Embolism	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Investigations Blood bilirubin Increased	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Investigations Blood Creatinine increased	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Renal and urinary disorders Acute Kidney Injury	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Renal and urinary disorders Haematuria	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Blood and lymphatic system disorders Anemia	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Cardiac disorders Atrial Fibraltion	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Hepatobiliary disorders Hyperbilirubinemia	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Infections and infestations Urinary tract Infection	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Nervous system disorders Dizziness	16.7% 1/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Psychiatric disorders Confusional State	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/5 • 13 months Data is presented by overall study enrollment and not by cohort.	5.0% 1/20 • 13 months Data is presented by overall study enrollment and not by cohort.
Reproductive system and breast disorders Pelvic Pain	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/6 • 13 months Data is presented by overall study enrollment and not by cohort.	20.0% 1/5 • 13 months Data is presented by overall study enrollment and not by cohort.	0.00% 0/20 • 13 months Data is presented by overall study enrollment and not by cohort.