Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Pamiparib, Pamiparib capsule, PARP Inhibitor BGB-290
BGB-290 · 11 trials · 22 indications
PFS is defined as the time from randomization to progressive disease (PD) per Response Evaluation Criteria in Solid Tumors ( RECIST) Version 1.1 by investigator assessment or death due to any cause, whichever occurs first.
ORR is defined as the percentage of participants who achieved a best overall response of confirmed complete response (CR) or partial response (PR), assessed by IRC per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Events occurring on or after treatment on Day 1 will be classified using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Adverse events leading to treatment discontinuation will be listed.
A DLT is defined as one of the following toxicities occurring during the DLT assessment window: Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting \>7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting \> 3 days and requiring transfusion, or any decreased platelet count \<15,000/mm3/ \<15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)
A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date on or after first dose of study treatment or was worsening in severity from baseline (pretreatment) up to 30 days following permanent study treatment discontinuation or initiation of new anti-cancer therapy, whichever occurs first. An SAE is any untoward medical occurrence that, at any dose meets at least one of the following criteria: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is considered a significant medical AE based on medical judgment.
Modified DCR is defined as the percentage of participants with complete response (CR), partial response (PR) or stable disease (SD) per RANO criteria as the response assessment at the end-of-treatment (EOT) visit.
ORR (objective response rate) is defined as percentage of participants with best overall response of CR or PR per RANO criteria (confirmed by a subsequent tumor assessment at least four weeks apart).
Data shows the number of participants who received treatment for the given number of cycles.
The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).
A DLT is defined as one of the following toxicities occurring during the DLT assessment window: Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting \>7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting \> 3 days and requiring transfusion, or any decreased platelet count \<15,000/mm3/ \<15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.03
ORR is defined as the percentage of participants who have a best overall response (BOR) of complete response (CR) or partial response (PR) based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where BOR is defined as the best response recorded from the first postbaseline tumor assessment until data cutoff date, disease progression or start of new anticancer treatment.
A TEAE is defined as an adverse event (AE) that had an onset date on or after the first dose of study drug up to 30 days following study drug discontinuation or was worsening in severity from baseline (pretreatment).
ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response
The primary endpoint of the study was a composite response rate that included ORR, a ≥50% decrease in serum prostate-specific antigen (PSA), and/or a decrease in circulating tumor cells.
The primary endpoint of the study was a composite response rate that included ORR, a ≥50% decrease in serum prostate-specific antigen (PSA), and/or a decrease in circulating tumor cells.
Primary PK parameter is area under the plasma concentration time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUClast).
Primary PK parameter is area under plasma concentration time curve (AUC).
Primary PK parameter is maximum observed plasma concentration (Cmax).
Total and unbound pamiparib concentration in enhancing and non-enhancing tumor tissue.
| Arm | Type | Description |
|---|---|---|
| Treatment arm | EXPERIMENTAL | - |
| Placebo arm | PLACEBO_COMPARATOR | - |
| Pamiparib | EXPERIMENTAL | Participants received pamiparib orally. |
| Placebo | PLACEBO_COMPARATOR | Participants received placebo orally. |
| Cohort 1: Triple-negative breast cancer (TNBC) | EXPERIMENTAL | Locally advanced or metastatic TNBC |
| Cohort 2: HR(+)/HER2(-) breast cancer | EXPERIMENTAL | Locally advanced or metastatic Hormone receptor-positive(HR+) human epidermal growth factor receptor2 Negative(HER2-) breast cancer |
| Arm A (Pamiparib (BGB-290), Temozolomide (TMZ)) | EXPERIMENTAL | Participants with grades III-IV newly diagnosed IDH1/2 mutant glioma receive 60mg pamiparib (BGB-290) PO BID on days 1-28 and 20mg temozolomide (TMZ) PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. |
| Arm B (BGB-290, Temozolomide) | EXPERIMENTAL | Participants with grades I-IV recurrent IDH1/2 mutant glioma receive 60mg PARP inhibitor pamiparib (BGB-290) PO BID on days 1-28 and 20mg temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Cohort B0: Participants who are surgical candidates with grades I-IV recurrent IDH1/2 mutant glioma receive 60mg PARP inhibitor BGB-290 PO BID for 7 days, pre-surgery. After recovery from surgery, participants receive PARP inhibitor BGB-290 PO BID on days 1-28 and 20mg temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. |
| Part A (core phase) | EXPERIMENTAL | 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) |
| Part B (core phase) | EXPERIMENTAL | 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 |
| Extension phase | EXPERIMENTAL | 60 mg pamiparib orally twice a day in 28-day cycles until progression of disease |
| Arm A (Dose Escalation) | EXPERIMENTAL | Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy. |
| Arm B (Dose Escalation) | EXPERIMENTAL | Participants with newly diagnosed unmethylated GBM will receive Pamiparib, radiation therapy (RT) and temozolomide (TMZ). |
| Arm A (Dose Expansion) | EXPERIMENTAL | Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy. |
| Arm C (Dose Escalation) | EXPERIMENTAL | Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ. |
| Arm C (Dose Expansion-Cohorts C1 and C2) | EXPERIMENTAL | Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ. |
| Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7) | EXPERIMENTAL | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7) | EXPERIMENTAL | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7) | EXPERIMENTAL | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7) | EXPERIMENTAL | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 100 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7) | EXPERIMENTAL | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 120 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14) | EXPERIMENTAL | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 14 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28) | EXPERIMENTAL | Pamiparib 60 mg twice daily in combination with TMZ 20 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28) | EXPERIMENTAL | Pamiparib 60 mg twice daily in combination with TMZ 40 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle |
| Dose Expansion: Gastric Cancer | EXPERIMENTAL | Participants with gastric or gastroesophageal junction cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
| Dose Expansion: Ovarian Cancer | EXPERIMENTAL | Participants with ovarian cancer, fallopian cancer, or primary peritoneal cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
| Dose Expansion: SCLC | EXPERIMENTAL | Participants with Small Cell Lung Cancer (SCLC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
| Dose Expansion: TNBC | EXPERIMENTAL | Participants with triple negative breast cancer (TNBC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
| Dose Expansion: Other HRD+ Cancers | EXPERIMENTAL | Participants with non-small cell lung cancer (NSCLC), esophageal cancer, squamous head and neck cancer, or soft tissue sarcomas whose tumors are homologous recombination deficiency (HRD)+ received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
| Phase 1: 20 milligram (mg) pamiparib | EXPERIMENTAL | 20 mg pamiparib twice a day for 21 days |
| Phase 1 : 40 mg pamiparib | EXPERIMENTAL | 40 mg pamiparib twice a day for 21 days |
| 60 mg pamiparib | EXPERIMENTAL | 60 mg pamiparib twice a day for 21 days |
| 60 mg pamiparib in platinum-sensitive ovarian cancer (PSOC) | EXPERIMENTAL | 60 mg pamiparib twice a day until occurrence of unacceptable toxicities, disease progression, withdrawal of consent or investigator discretion |
| 60 mg pamiparib in platinum resistant ovarian cancer (PROC) | EXPERIMENTAL | 60 mg pamiparib twice a day until occurrence of unacceptable toxicities, disease progression, withdrawal of consent or investigator discretion |
| ovarian cancer, fallopian cancer, or primary peritoneal cancer | EXPERIMENTAL | 60mg BID oral. |
| Breast Cancer | EXPERIMENTAL | 60mg BID Ora |
| Prostate Cancer | EXPERIMENTAL | 60mg BID Oral |
| Small Cell Lung Cancer | EXPERIMENTAL | 60mg BID Oral |
| Gastric Cancer | EXPERIMENTAL | 60mg BID Oral |
| Arm A Newly-diagnosed Glioblastoma Participant treated with Pamiparib | EXPERIMENTAL | Participants undergoing resection for a presumed newly diagnosed glioblastoma (nGBM) will be treated with pamiparib for 4 days prior to surgical resection. Patients who proceed to Phase 2 will receive pamiparib administered orally BID continuously in combination with 6-7 weeks of radiation therapy and pamiparib in combination with TMZ in the maintenance phase. |
| Arm B Recurrent Glioblastoma Participant treated with Pamiparib | EXPERIMENTAL | Recurrent glioblastoma (rGBM) patients who are scheduled for surgery and expected to receive postoperative fractionated radiotherapy (RT) will be treated with pamiparib for 4 days prior to surgical resection. Patients who proceed to Phase 2 will receive pamiparib administered orally BID continuously in combination with 6-7 weeks of radiation therapy and pamiparib in combination with TMZ in the maintenance phase. |
| Arm C Recurrent Glioblastoma Participant treated with Olaparib | EXPERIMENTAL | Arm C will be an exploratory arm in recurrent glioblastoma patients (rGBM) treated with Olaparib for 4 days prior to surgical resection. Patients who proceed to Phase 2 will receive olaparib administered orally BID continuously in combination with 6-7 weeks of radiation therapy and pamiparib in combination with TMZ in the maintenance phase. |
| Name | Type | Description |
|---|---|---|
| Pamiparib capsule | DRUG | 60 mg twice daily (BID), orally (per os-PO) |
| Placebo capsule | DRUG | 60mg BID, PO |
| Pamiparib | DRUG | 60 mg orally twice daily |
| Placebo | DRUG | 60 mg orally twice daily |
| BGB-290 | DRUG | Administered orally |
| PARP Inhibitor BGB-290 | DRUG | Given PO |
| Temozolomide (TMZ) | DRUG | Given PO |
| [14C]-pamiparib | DRUG | During the treatment phase, pamiparib 60 mg administered orally twice daily |
| pamiparib 60 mg | DRUG | Single dose of 60 mg pamiparib orally on Days 1 and 10 |
| pamiparib 20 mg | DRUG | Single dose of 20 mg pamiparib orally on days 1 and 7 |
| itraconazole | DRUG | 200 mg itraconazole once a day al Day 3 to day 8 |
| rifampin | DRUG | 600 mg rifampin once a day from days 3 to 11 |
| TMZ | DRUG | Administered as specified in the treatment arm |
| Radiation | RADIATION | Up to 60 Gy (total) over 6 - 7 weeks |
| Temozolomide | DRUG | TMZ at various doses administered by mouth as a capsule once daily. |
| Olaparib | DRUG | 200mg administered orally BID for 4 days prior to surgical resection |
| Radiation therapy | RADIATION | Patients in Phase 2 will receive 6-7 weeks of radiation therapy per standard of care |
Key Inclusion Criteria: 1. Histologically diagnosed high-grade serous or endometrioid ovarian cancer (including primary peritoneal and fallopian tube cancer) 2. Completion of ≥2 previous platinum-containing regimens (eg, carboplatin or cisplatin) 3. Complete response (CR) or partial response (PR) a...
BGB-290 is an investigational small molecule being developed by BeOne Medicines Ltd. for cancer treatment. It is a PARP1 and PARP2 inhibitor studied in advanced solid tumors and HER2-negative breast cancer. It has been evaluated in clinical trials in Australia and China and is not approved for commercial use.
BGB-290 has been studied in HER2-negative breast cancer, specifically in patients with BRCA mutations. A completed Phase 2 trial in China evaluated its efficacy and safety in metastatic HER2-negative breast cancer patients with BRCA mutations. It remains investigational and is not approved for this or any other indication.
BGB-290 targets PARP1 and PARP2, which are enzymes involved in DNA repair. By inhibiting these enzymes, BGB-290 interferes with the ability of cancer cells to repair damaged DNA. This mechanism is being investigated for treating advanced solid tumors and HER2-negative breast cancer.
BGB-290 is being developed by BeOne Medicines Ltd., which trades under the ticker ONC. The company has sponsored clinical trials of BGB-290 in Australia and China for advanced solid tumors and HER2-negative breast cancer.
BGB-290 is in Phase 1 clinical development according to its overall program status, though a Phase 2 trial has also been completed. It is investigational and has not been approved by the FDA or any regulatory agency for commercial use.
BGB-290 has been evaluated in two completed clinical trials. NCT02361723 was a Phase 1a/1b study in advanced solid tumors that had failed previous treatments, conducted in Australia with 101 participants. NCT03575065 was a Phase 2 trial in metastatic HER2-negative breast cancer with BRCA mutations in China, enrolling 88 patients.