PDR001 Plus Imatinib for Metastatic or Unresectable GIST

• Status: Recruiting
• Trial end date: 2022-08-30
• Target enrollment: 0
• Participant gender: All

Summary

Assuming that PDR001, an anti-PD-1 antibody, with imatinib might be effective in advanced GIST after failure of standard TKI therapies including imatinib, sunitinib, and regorafenib. In this phase I/II study of PDR001 plus imatinib, it is aimed to evaluate the safety and efficacy of this regimen as 4th line of treatment in advanced GIST.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Asan Medical Center
• Collaborator: Novartis
• Treatments: Imatinib Mesylate; Spartalizumab

Criteria

1. Age 18 years or older, at the time of acquisition of informed consent

2. Histologically confirmed metastatic or unresectable GIST with CD117(+), DOG-1(+), or mutation in KIT or PDGFRαgene

3. Disease control (response or stabilization for at least 6 months) with first-line imatinib and failure (progression) to imatinib, sunitinib, and regorafenib. Disease progression is defined as (1) size increase ≥ 20% by RECIST version 1.1, (2) appearance of a definite new lesion (excluding small cystic new lesions in the liver within 6 months of starting TKIs), (3) new solid nodule ≥ at least 2 cm in size within a cystic mass, or (4) increase of the size ( ≥ 20%) of previously existing solid nodule ≥ at least 2 cm in size within a cystic mass.

4. ECOG performance status of 0-2

5. Resolution of all toxic effects of prior treatments to grade 0 or 1 by NCI-CTCAE version 4.0

6. At least one measurable lesion by RECIST version 1.1.

7. Adequate bone marrow, hepatic, renal, and other organ functions

• Neutrophil ≥ 1,500/mm3

• Platelet ≥ 75,000/mm3

• Hemoglobin ≥ 8.0 g/dL

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

• AST/ALT ≤ 3 x ULN without liver metastases or AST/ALT ≤ 5 x ULN with liver metastases

• Creatinine≤ 1.5 x ULN

8. Women with reproductive potential must have a negative serum or urine pregnancy test

9. Washout period of previous TKIs or chemotherapy for more than 4 times the half-life (Seven days of washout period is enough for imatinib, sunitinib, and regorafenib).

10. No prior use of PDR001 or other immune check point inhibitors

11. Provision of a signed written informed consent

Exclusion criteria

1. Patients who are intolerant to imatinib

2. Women of child-bearing potential who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control.

3. Impaired cardiac function or clinically significant cardiac disease, including any of the following:

Clinically significant and/or uncontrolled heart disease such as congestive heart failure (CHF) requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia

• Congenital long QT syndrome

• QTc> 470 msec on screening ECG

• Unstable angina pectoris ≤ 3 months prior to starting study drug

• Acute Myocardial Infarction ≤ 3 months prior to starting study drug

4. Uncontrolled infection

5. History of severe hypersensitivity reactions to other monoclonal antibodies

6. Active autoimmune disease or a documented history of autoimmune disease, or any condition that requires systemic steroids, except vitiligo or resolved asthma/atopy that is treated with broncho-dilators (e.g., albuterol).

7. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for this study

8. Major surgery ≤ 28 days prior to starting study drug or who have not recovered from side effects of such therapy

9. Known diagnosis of HIV infection (HIV testing is not mandatory)

10. History of another primary malignancy that is currently clinically significant or currently requires active intervention

11. Patients with brain metastases as assessed by radiologic imaging (e.g. CT, MRI) due to symptoms clinically suspected of brain metastases

12. Alcohol or substance abuse disorder

13. Active HBV and HCV infections requiring therapy: patients with undetectable HBV DNA level under the anti-viral agents are allowed to be enrolled.