Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer

BeiGene

Status and phase: Completed; Phase 1

Conditions: Solid Tumor

Treatments: Drug: itraconazole; Drug: pamiparib 60 mg; Drug: rifampin; Drug: pamiparib 20 mg; Drug: pamiparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03994211

2019-000112-28 (EudraCT Number)

BGB-290-105

Details and patient eligibility

About

The study was an open-label, parallel-group, fixed-sequence study in male and female cancer patients. The study consists of 2 phases: the Core Phase, which is divided into Part A and Part B, and the Extension Phase. Part A investigated the effect of CYP3A induction by rifampin on the single dose pharmacokinetics (PK) of pamiparib, and Part B investigated the effect of CYP3A inhibition by itraconazole on the single dose PK of pamiparib. Participants were offered participation in the Extension Phase, in which they received pamiparib until progression of disease, unacceptable toxicity, withdrawal of consent, or any other reason for discontinuation.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Age ≥ 18 years
2. Histologically or cytologically confirmed advanced or metastatic solid tumors that are refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
3. Disease that is evaluable per RECIST Version 1.1 or Prostate Cancer Working Group-3 (PCWG-3)
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
5. Life expectancy ≥ 12 weeks
6. Adequate hematologic and end-organ function

Key Exclusion Criteria:

1. History of hypersensitivity to rifampin, any rifamycin or any of the components of the rifampin capsule (Part A).

2. History of hypersensitivity to itraconazole or any of the components of the itraconazole capsule (Part B).

3. Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor at therapeutic doses is allowed, provided that such treatment was not the most recent therapy (PARP inhibitor must have been discontinued ≥ 3 months prior to the first dose of pamiparib):

   • Participants who experienced prior severe toxicity to PARP inhibitors that in the opinion of the investigator precludes further treatment with PARP inhibitors should be excluded

4. Diagnosis of Myelodysplastic syndrome (MDS)

5. Active infection requiring systemic treatment

6. Any of the following cardiovascular criteria:

   1. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before Day 1 of pamiparib administration

   2. Symptomatic pulmonary embolism ≤ 28 days before Day 1 of pamiparib administration

   3. Any history of acute myocardial infarction ≤ 6 months before Day 1 of pamiparib administration

   4. Any history of heart failure meeting New York Heart Association Classification III or IV ≤ 6 months before Day 1 of pamiparib

      • Participants with congestive heart failure or history of heart failure should be excluded from Part B (itraconazole)

   5. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before Day 1 of pamiparib administration

   6. Any history of cerebral vascular accident ≤ 6 months before Day 1 of pamiparib administration

7. Previous complete gastric resection or lap-band surgery, chronic diarrhea, active inflammatory gastrointestinal disease, known diverticular disease or any other disease-causing malabsorption syndrome

   • Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed

8. Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena ≤ 6 months before Day 1 of pamiparib administration

9. Use or anticipated need for food or drugs known to be strong or moderate CYP3A inhibitors or strong CYP3A inducers ≤ 14 days (or ≤ 5 half-lives if half-life is known) prior to Day 1 of pamiparib administration

10. Known history of intolerance to the excipients of the pamiparib capsule

11. Have known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 3 patient groups

Part A (core phase)

Experimental group

Description:

60 mg pamiparib administered orally on Days 1 and 10 fasting 8 hours pre-dose 600 mg rifampin once a day from days 3 to 11 in the fasted state (at least 2 hours predose)

Treatment:

Drug: rifampin

Drug: pamiparib 60 mg

Part B (core phase)

Experimental group

Description:

Single dose of 20 mg pamiparib orally in the fasted state (at least 8 hours predose) on days 1 and 7 200 mg itraconazole once a day approximately 30 minutes after completing a meal Day 3 to day 8

Treatment:

Drug: pamiparib 20 mg

Drug: itraconazole

Extension phase

Experimental group

Description:

60 mg pamiparib orally twice a day in 28-day cycles until progression of disease

Treatment:

Drug: pamiparib