A phase 1/2, open-label, study to determine the safety and preliminary efficacy of APR-246 in combination with pembrolizumab in subjects with solid tumor malignancies. The study will include a safety lead-in portion followed by a phase 2 expansion portion in specific disease groups.
This is a phase 1/2, open-label, study to determine the safety and preliminary efficacy of
APR-246 (eprenetapopt) in combination with pembrolizumab in subjects with solid tumor
malignancies. In the safety lead-in part of study (phase 1), the safety and the recommended
phase 2 dose (RP2D) of APR-246 will be investigated.
In the expansion part of the study (phase 2), both safety and efficacy for the combination
therapy will be investigated in the 3 cohorts.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||June 25, 2020||Phase 1/Phase 2||Interventional|
Primary Outcome 1 - Measure: To evaluate the safety and tolerability of APR-246 in combination with pembrolizumab in subjects with solid tumors.
Primary Outcome 1 - Time Frame: Through study completion, approximately 1 year
Primary Outcome 2 - Measure: To confirm the maximum tolerated dose (MTD) for APR-246 in combination with pembrolizumab
Primary Outcome 2 - Time Frame: Through safety lead in period, approximately 6 months
1. Signed informed consent form (ICF) and ability to comply with protocol requirements.
2. Known tumor TP53 mutation status from recent or archival sample.
3. Histologically and/or cytologically confirmed solid tumor malignancy
1. Safety lead in- Advanced non-central nervous system (CNS) primary tumors that
have progressed after first line treatment, who are intolerant to first line
treatment, or who are unable to receive first line treatment, and for whom
pembrolizumab, or pembrolizumab-based therapy is considered appropriate
2. Expansion 1- Patients with a confirmed diagnosis of advanced gastric or
gastroesophageal junction (GEJ) tumors that have progressed after first line
treatment, who are intolerant to first line treatment, or who are unable to
receive first line treatment
3. Expansion 2- Patients with a confirmed diagnosis of advanced bladder/urothelial
tumors that have progressed after first line treatment, or who are intolerant to
first line treatment, or who are unable to receive first line treatment with
4. Expansion 3- Confirmed diagnosis of advanced non-small cell lung cancer (NSCLC)
previously treated with anti-PD-1 or anti-PD-L1 therapy.
4. Adequate organ function
1. Creatinine clearance > 30 mL/min
2. Total serum bilirubin < 1.5 × upper limit of normal (ULN) unless due to Gilbert's
syndrome, tumor involvement, hemolysis or considered an effect of regular blood
3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 × ULN,
unless due to involvement by the underlying malignancy.
5. Projected life expectancy of ≥ 12 weeks.
6. Age ≥ 18 years at the time of signing the ICF.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
8. In the expansion portion, measurable disease meeting the following criteria:
1. At least 1 lesion of ≥10 mm in the longest diameter (LD) for a non-lymph node or
≥15 mm in the short-axis diameter for a lymph node that is serially measurable
according to RECIST 1.1.
2. Lesions that have had external beam radiotherapy or loco-regional therapies such
as radiofrequency ablation must show subsequent evidence of substantial size
increase (ex. 20% increase in LD) to be deemed a target lesion.
9. Negative serum or urine pregnancy test prior to study treatment initiation in female
subjects of childbearing potential.
10. Women of childbearing potential and men with female partners of childbearing potential
must be willing to use an effective form of contraception
1. Known history of untreated human immunodeficiency virus (HIV)/HIV with a detectable
viral load or active hepatitis B or active hepatitis C infection.
2. Cardiac abnormalities
3. Concomitant malignancies or previous malignancies with less than a 1-year disease-free
interval at the time of signing consent.
4. Pregnancy or lactation.
5. Active uncontrolled systemic infection.
6. An autoimmune condition requiring ≥ 10 mg (or equivalent corticosteroid) prednisone
daily, or any other systemic immunosuppressive treatment within 28 days of first dose
of study therapy.
7. Known history of active tuberculosis.
8. Current (non-infectious) pneumonitis, or a history of pneumonitis that required
9. A live vaccine administered within 30 days of the first dose of study treatment.
10. Receipt of any investigational product within 14 days or 5 half-lives prior to study
treatment initiation, whichever is shortest.
11. Prior intolerance to pembrolizumab or other anti-PD-1/PD-L1 agents.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Joachim Gullbo, MD
Role: Study Director
Affiliation: Theradex Oncology
Name: Eyal Attar, MD
Phone: +1 617 804 6947
Saint Louis, Missouri 63130