A Study of APG-1252 in Patients With SCLC or Other Solid Tumors



Status:Recruiting
Conditions:Lung Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:3/17/2019
Start Date:February 12, 2017
End Date:September 12, 2019
Contact:Isabel Jimenez, RN, MSN
Email:isabel.jimenez@start.stoh.com
Phone:210-593-5265

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A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Intravenously Administered APG-1252 in Patients With Small Cell Lung Cancer (SCLC) or Other Solid Tumors

APG-1252 is a highly potent Bcl-2 family protein inhibitor, a promising drug candidate which
shown high binding affinities to Bcl-2, Bcl-xL and Bcl-w. The preclinical studies have shown
that APG-1252 alone achieves complete and persistent tumor regression in multiple tumor
xenograft models with a twice weekly or weekly dose-schedule, including SCLC, colon, breast
and ALL cancer xenografts; achieves strong synergy with the chemotherapeutic agents,
indicating that APG-1252 may have a broad therapeutic potential for the treatment of human
cancer as a single agent and in combination with other classes of anticancer drugs. APG-1252
is intended for the treatment of patients with SCLC or other solid tumors.

This is a multi-center, open-label, dose escalation Phase I study to determine the MTD and
DLTs of intravenously administered APG-1252. After dose escalation to 240mg twice weekly, 2
dose cohorts two different dosing schedules including weekly and twice weekly will be
assessed to evaluate for safety, tolerability, PK and preliminary anti-tumor efficacy.
Treatment with APG-1252 will be administered to 30-60 patients at approximately 2
investigational sites in US.

In dose cohort 1, patients will be treated in cycles, which are defined by APG-1252
intravenous administration on Days 1, 4, 8, 11, 15, 18 and 22, over a 28-day cycle the start
dose is 10mg.

After dose escalation to 240mg twice weekly in dose cohort 1, dose cohort 2 will be performed
with dose cohort 1 parallelly, patients will be treated in the same 28-day-cycles, APG-1252
intravenous administration on Days 1, 8, 15, and 22, the start dose is 240mg.

In both dose cohorts' patients could continue to receive cycles of APG-1252 until disease
progress or unacceptable toxicity.

Study drug will be administered by intravenous infusion for 30 minutes at the investigational
site by site staff.

Inclusion Criteria:

1. Histologically or cytologically confirmed small cell lung cancer (SCLC) or other solid
tumors;

2. Male or non-pregnant, non-lactating female patients age ≥18 years;

3. Locally advanced or metastatic disease for which no standard therapy is judged
appropriate by the investigator;

4. Eastern Cooperative Oncology Group (ECOG) Performance Status < 2;

5. Adequate hematologic function as indicated by:

1. Platelet count ≥ 100,000/mm3

2. Hemoglobin ≥ 9.0g/dL Platelet count ≥ 100,000/mm3

3. Absolute neutrophil count (ANC) ≥1000/µL

6. Adequate renal and liver function as indicated by:

1. Serum creatinine ≤ 1.5 x upper limit of normal (ULN); if serum creatinine is >1.5
X ULN, creatinine clearance must be ≥ 50 mL/min (see Section 22.3).

2. Total bilirubin ≤1.5 x ULN; If Gilbert's Syndrome may have Bilirubin> 1.5 x ULN

3. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤3 x ULN of
institution's normal range; for patients with known liver metastases, AST and ALT
may be ≤ 5 x ULN.

4. Coagulation: aPTT and PT<1.2 x the upper limit of normal

7. Brain metastases with clinically controlled neurologic symptoms, defined as surgical
excision and/or radiation therapy followed by 21 days of stable neurologic function &
no evidence of CNS disease progression as determined by CT or MRI within 21 days prior
to the first dose of study drug.

8. Willingness to use contraception by a method that is deemed effective by the
investigator by both males and female patients of child bearing potential
(postmenopausal women must have been amenorrheal for at least 12 months to be
considered of non-childbearing potential) and their partners throughout the treatment
period and for at least three months following the last dose of study drug;

9. Ability to understand and willingness to sign a written informed consent form (the
consent form must be signed by the patient prior to any study-specific procedures);

10. Willingness and ability to comply with study procedures and follow-up examination.

Exclusion Criteria:

1. Receiving concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
immunotherapy, hormonal therapy, targeted therapy, biologic therapy, with the
exception of hormones for hypothyroidism or estrogen replacement therapy (ERT), anti
estrogen analogs, agonists required to suppress serum testosterone levels); or any
investigational therapy, or has had tumor embolization or tumor lysis syndrome (TLS)
within 14 days prior to the first dose of study drug.

2. Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of
study drug.

3. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not
recover to < Grade 2;

4. Known bleeding diathesis/disorder;

5. Recent history of non-chemotherapy induced thrombocytopenia associated bleeding within
1 year prior to first dose of study drug.

6. Have active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia
(AIHA), or a history of being refractory to platelet transfusions (within 1 year prior
to the first dose of study drug).

7. Serious gastrointestinal bleeding within 3 months;

8. Use of therapeutic doses of anti-coagulants is excluded, along with anti-platelet
agents; low-dose anticoagulation medications that are used to maintain the patency of
a central intravenous catheter are permitted.

9. Received a biologic (G-CSF, GM-CSF or erythropoietin) within 28 days prior to the
first dose of study drug.

10. Failure to recover adequately, as judged by the investigator, from prior surgical
procedures. Patients who have had major surgery within 28 days from study entry, and
patients who have had minor surgery within 14 days of study entry;

11. Unstable angina, myocardial infarction, or a coronary revascularization procedure
within 180 days of study entry.

12. Neurologic instability per clinical evaluation due to tumor involvement of the central
nervous system (CNS). Patients with CNS tumors that have been treated, are
asymptomatic and who have discontinued steroids (for the treatment of CNS tumors) for
>28 days may be enrolled;

13. Active symptomatic fungal, bacterial and/or viral infection including, but not limited
to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C);

14. Diagnosis of fever and neutropenia within 1 week prior to study drug administration.

15. Uncontrolled concurrent illness including, but not limited to: serious uncontrolled
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
the study requirements.

16. Prior treatment with Bcl-2/Bcl-xL inhibitors.

17. Any other condition or circumstance of that would, in the opinion of the investigator,
make the patient unsuitable for participation in the study.

18. Known clinically active hepatitis B or hepatitis C infection. Testing for hepatitis B
and C is not required for study enrollment.

19. Known HIV infection.
We found this trial at
2
sites
Grand Rapids, Michigan 49503
Principal Investigator: Nehal Lakhani, M.D., Ph.D.
Phone: 616-954-5554
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Grand Rapids, MI
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San Antonio, Texas 78229
Principal Investigator: Drew Resco, M.D.
Phone: 210-593-5265
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San Antonio, TX
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