BeiGene Presents Clinical Data from Two Phase 2 Trials of Pamiparib at the 2021 ASCO Annual Meeting
Pamiparib, a potent and selective PARP1 and PARP2 inhibitor, demonstrated meaningful and durable efficacy in patients with advanced HER2-negative breast cancer
Pamiparib showed numerically higher progression-free survival in patients with gastric cancer compared to placebo, although the results did not achieve statistical significance
Pamiparib was generally well-tolerated across both trials
Pamiparib was recently approved in
“We are pleased to share results from our pamiparib clinical development program, focused on diseases with high prevalence, as we work towards our mission of improving outcomes for patients in need,” commented
Results from Phase 2 Trial of Pamiparib in Locally Advanced or Metastatic HER2-Negative Breast Cancer with gBRCAm
Poster No. 1087
This single-arm, open label, multi-center Phase 2 trial (NCT03575065) was designed to evaluate the safety and efficacy of pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer, with deleterious or suspected deleterious gBRCA1/2m, who received no more than two prior lines of chemotherapy. A total of 88 patients were enrolled, including 62 patients with triple-negative breast cancer (TNBC cohort) and 26 patients with hormone receptor-positive (HR[+]) and HER2(-) breast cancer (HR[+] cohort). Fifty-five patients in the TNBC cohort and 21 patients in the HR(+) cohort had measurable disease at baseline per independent review committee (IRC). The primary endpoint of the trial was objective response rate (ORR) as assessed by IRC per RECIST v1.1; secondary endpoints included investigator-assessed ORR, duration of response (DoR), best overall response (BOR), progression-free survival (PFS), clinical benefit rate (CBR), and disease control rate (DCR) as assessed by IRC and investigator, and overall survival (OS), as well as safety and tolerability.
“Studies have suggested that breast cancer with germline BRCA mutations may be susceptible to PARP inhibition. These Phase 2 results demonstrated pamiparib’s efficacy in patients with HR(+)/HER2(-) breast cancer, as well as in triple-negative breast cancer, one of the most aggressive forms of the disease with the poorest outcomes,” said
At the data cut-off on
Pamiparib demonstrated meaningful and durable clinical activity in patients across both cohorts. Efficacy results included:
- Confirmed ORR as assessed by IRC, the primary efficacy endpoint, was 61.9% (95% CI: 38.4, 81.9) in the HR(+) cohort and 38.2% (95% CI: 25.4, 52.3) in the TNBC cohort;
- Four patients achieved a complete response (CR), including three in the TNBC cohort and one patient in the HR(+) cohort;
- 18 patients in the TNBC cohort and 12 patients in the HR(+) cohort demonstrated a partial response (PR);
- DCR as assessed by IRC was 90.5% (95% CI: 69.6, 98.8) in the HR(+) cohort and 72.7% (95% CI: 59.0, 83.9) in the TNBC cohort;
- Additionally, CBR as assessed by IRC was 71.4% (95% CI: 47.8, 88.7) in the HR(+) cohort and 43.6% (95% CI: 30.3, 57.7) in the TNBC cohort;
- Patients in the HR(+) cohort had a median DoR of 7.5 months (95% CI: 5.6, 14.8) and patients in the TNBC cohort had a median DoR of 7.0 months (95% CI: 3.9, not estimable [NE]);
- The median PFS was 9.2 months (95% CI: 7.4, 11.9) in the HR(+) cohort and 5.5 months (95% CI: 3.7, 7.3) in the TNBC cohort; and
- In the trial, the median OS in the TNBC cohort was 17.1 months (95% CI:13.7, NE) and was not reached in the HR(+) cohort (NE; 95% CI: 18.1, NE).
Pamiparib was generally well-tolerated, and results from the safety analysis for all 88 patients across both cohorts included:
- 87 patients (98.9%) experienced at least one treatment-emergent adverse event (TEAE) of any grade and 54 patients (61.4%) experienced at least one Grade ≥3 TEAE;
- 87 patients (98.9%) experienced at least one treatment-related TEAE of any grade, and 53 patients (60.2%) experienced at least one Grade ≥3 treatment-related TEAE, with the most common (≥5%) being anemia (39.8%), neutrophil count decrease (29.5%), white blood cell count decrease (21.6%), platelet count decrease (9.1%), leukopenia (5.7%), and neutropenia (5.7%);
- Serious TEAEs were reported in 19 patients (21.6%) and serious treatment-related TEAEs were reported in 15 patients (17.0%);
- Two patients experienced treatment discontinuation due to TEAEs, both considered treatment-related; and
- TEAEs leading to death occurred in one patient (1.1%) and no treatment-related TEAEs leading to death were reported.
Results from Phase 2 Trial of Pamiparib vs. Placebo in Locally Advanced or Metastatic Gastric Cancer
Poster No. 3109
PARALLEL 303 is a double-blind, randomized, multicenter Phase 2 trial (NCT03427814) comparing the safety and efficacy of pamiparib vs placebo as maintenance therapy in patients with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based first-line chemotherapy. A total of 136 patients were enrolled and due to slow enrollment and a change in the standard of care for this patient population, the trial did not meet the planned target enrollment of approximately 540 patients. Patients were randomized 1:1 to receive pamiparib 60 mg orally twice daily (n = 71) or placebo (n = 65) in 28-day cycles. The primary endpoint was PFS as assessed by investigator per RECIST v1.1; secondary endpoints included time to subsequent treatment (TSST), ORR, DoR, and time to response (TTR) as assessed by investigator, OS, and safety. At the time of data analysis, OS data were immature.
“Many patients with gastric cancer become resistant to currently available therapies in later stages of disease, so continued research is crucial to find medicines that may improve outcomes and survival,” said
At the data cutoff on
Pamiparib demonstrated a numerically higher median PFS of 3.7 months (95% CI, 1.9, 5.3 months), compared to 2.1 months (95% CI, 1.9, 3.8 months) in the placebo arm, however the trial did not achieve statistical significance (p=0.1428; HR=0.799 [95% CI, 0.5, 1.2]). Additional efficacy results included:
- The median OS in the pamiparib arm was 10.2 months (95% CI: 8.7, 16.3), compared to 12.0 months in the placebo arm (95% CI: 8.2, not estimable [NE]);
- The ORR in the pamiparib arm was 7.7% (95% CI: 1.6, 20.9), compared to 6.3% (95% CI: 0.8, 20.8) in the placebo arm;
- The median DoR in the pamiparib arm was 3.6 months (95% CI: 3.5, NE), compared to NE (95% CI: 5.6, NE) in the placebo arm; and
- The median TTR in the pamiparib arm was 3.7 months (range: 1.8, 7.3), compared to 1.9 months (range: 1.9, 1.9) in the placebo arm.
In the trial, pamiparib was generally well-tolerated, with no new safety signals observed. Safety results included:
- 65 patients (91.5%) experienced at least one TEAE of any grade in the pamiparib arm, compared to 61 patients (93.8%) in the placebo arm;
- Serious TEAEs and TEAEs of Grade ≥3 were reported in 14 patients (19.7%) and 29 patients (40.8%) respectively in the pamiparib arm, compared to 10 patients (15.4%) and 20 patients (30.8%) in the placebo arm;
- In the pamiparib arm, the most common (≥10%) TEAEs included anemia (36.6%), nausea (32.4%), decreased appetite (26.8%), vomiting (23.9%), asthenia (21.1%), diarrhea (18.3%), upper abdominal pain (16.9%), aspartate aminotransferase increased (AST; 12.7%), alanine aminotransferase increased (ALT; 11.3%), abdominal pain (11.3%), constipation (11.3%), and white blood cell count decreased (11.3%);
- In the placebo arm, the most common (≥10%) TEAEs included abdominal pain (18.5%), nausea (16.9%), peripheral sensory neuropathy (13.8%), asthenia (16.9%), anemia (12.3%), decreased appetite (12.3%), dysphagia (12.3%), upper abdominal pain (10.8%), constipation (10.8%), and diarrhea (10.8%);
- Treatment discontinuation due to TEAEs occurred in eight patients (11.3%) in the pamiparib arm, compared to two patients (3.1%) in the placebo arm; and
- Death due to TEAEs occurred in two patients (2.8%) in the pamiparib arm, none of which were deemed treatment-related, compared to two patients (3.1%) in the placebo arm, of which one (1.5%) was deemed treatment-related.
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Pamiparib is an inhibitor of PARP1 and PARP2 which has demonstrated pharmacological properties such as brain penetration and PARP-DNA complex trapping in preclinical models. Discovered by
About the Pamiparib Clinical Program
Clinical trials of pamiparib include:
Phase 3 trial in
Chinaof pamiparib as maintenance versus placebo in patients with platinum-sensitive recurrent ovarian cancer (NCT03519230);
- Phase 2 trial of pamiparib in patients with metastatic castration-resistant prostate cancer with homologous recombination deficiency (NCT03712930);
Phase 2 trial in
Chinaof pamiparib in patients with metastatic HER2-negative breast cancer with BRCA mutation (NCT03575065);
- Phase 2 trial of pamiparib in patients with advanced or inoperable gastric cancer (NCT03427814);
Phase 1/2 trial in
Chinaof pamiparib in patients with advanced ovarian cancer, fallopian cancer, and primary peritoneal cancer or advanced triple negative breast cancer (NCT03333915);
- Phase 1b/2 trial of pamiparib in combination with radiation therapy and/or temozolomide in patients with first-line or recurrent/refractory glioblastoma (NCT03150862);
- Phase 1b trial of pamiparib in combination with temozolomide in patients with locally advanced or metastatic solid tumors (NCT03150810); and
- Phase 1b trial of pamiparib in combination with tislelizumab for a variety of solid tumor malignancies (NCT02660034).
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding data from the clinical trials of pamiparib presented in this press release, the potential for pamiparib to provide clinical benefit or advantages in safety and tolerability to patients,
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