BeiGene Presents Data at ESMO Virtual Congress 2020 on Phase 3 Trial of Tislelizumab in First-Line Non-Squamous Non-Small Cell Lung Cancer and Phase 2 Trial of Pamiparib in Advanced Ovarian Cancer
Sep 17, 2020 6:05 PM
“We are pleased to share the promising RATIONALE 304 results, which were used to support our recently accepted supplemental new drug application in first-line non-squamous NSCLC in China,” commented
“In addition to our Phase 3 data on tislelizumab, we are glad to report that the pivotal Phase 2 data of pamiparib in advanced ovarian cancer patients with BRCA1/2 mutations demonstrated high objective response rates in both platinum-sensitive and platinum-resistant subtypes, and we look forward to advancing pamiparib, which is currently under regulatory review in China,” added
RATIONALE 304, Phase 3 Trial of Tislelizumab in Combination with Chemotherapy in First-Line Locally Advanced or Metastatic Non-Squamous NSCLC
Poster #1263P
“Tislelizumab in combination with pemetrexed and platinum chemotherapy has demonstrated encouraging results among advanced NSCLC patients with non-squamous histology, including a median progression-free survival of 9.7 months and an overall response rate of 57.4 percent. We are hopeful that tislelizumab can bring a new treatment option to patients with lung cancers in China,” commented
RATIONALE 304 is a randomized, open-label, multi-center Phase 3 clinical trial of tislelizumab in combination with pemetrexed and platinum chemotherapy (either carboplatin or cisplatin) as a first-line treatment for patients with stage IIIB or stage IV non-squamous NSCLC, compared to pemetrexed and platinum alone (NCT03663205). A total of 334 patients in
- The trial achieved the primary endpoint of progression-free survival (PFS) as assessed by independent review committee (IRC), with a median of 9.7 months in Arm A, a significant improvement compared to 7.6 months in the chemotherapy alone Arm B (p=0.0044; stratified hazard ratio [HR]=0.645 [95% CI: 0.462, 0.902]);
- Higher objective response rate (ORR) and disease control rate (DCR) were achieved in patients who received tislelizumab in combination with chemotherapy as assessed by IRC per RECIST v1.1 – 57.4% (95% CI: 50.6, 64.0) and 89.2% (95% CI: 84.4, 93.0) in Arm A, compared to 36.9% (95% CI: 28.0, 46.6) and 81.1% (95% CI: 72.5, 87.9) in Arm B;
- Longer duration of response (DoR) was observed in patients who received tislelizumab in combination with chemotherapy, with a median of 8.5 months (95% CI: 6.80, 10.58) in Arm A, compared to 6.0 months (95% CI: 4.99, not evaluable) in Arm B;
- Treatment of tislelizumab in combination with platinum and pemetrexed was generally well-tolerated, with no new safety signals identified;
- All patients in Arm A and 99.1% of patients in Arm B experienced at least one treatment-emergent adverse event (TEAE); TEAEs leading to permanent discontinuation of any component of treatment occurred in 25.7% and 9.1% of the patients in Arm A and Arm B, respectively;
-
Most treatment-related adverse events (TRAEs) were hematologic in nature and primarily mild-to-moderate in severity, as follows:
- In Arm A, the most common (≥20.0%) Grade 1-2 TRAEs include anemia (68.0%), leukopenia (60.8%), thrombocytopenia (50.5%), nausea (42.3%), increased alanine aminotransferase (ALT; 41.4%), increased aspartate aminotransferase (AST; 38.7%), neutropenia (37.4%), fatigue (33.3%), decreased appetite (28.4%), and vomiting (24.8%);
- In Arm B, the most common (≥20.0%) Grade 1-2 TRAEs include anemia (64.5%), leukopenia (59.1%), thrombocytopenia (50.0%), increased AST (44.5%), increased ALT (40.9%), nausea (39.1%), neutropenia (38.2%), fatigue (31.8%), decreased appetite (25.5%), and vomiting (20.9%);
- Grade ≥3 TRAEs occurred in 67.6% of patients in Arm A and 53.6% in Arm B, with the most common (≥10.0%) in Arm A being neutropenia (44.6%), leukopenia (21.6%), thrombocytopenia (19.4%), and anemia (13.5%), and the most common (≥10.0%) in Arm B being neutropenia (35.5%), leukopenia (14.5%), thrombocytopenia (13.6%), and anemia (10.0%);
- Immune-mediated AEs were reported in 57 patients in Arm A (25.7%), and most of them were mild-to-moderate in severity, with the most common ones being pneumonitis (9%), hypothyroidism (8.6%), and hyperthyroidism (2.7%); and
- Across the trial, nine patients experienced a fatal TEAE, including seven in Arm A caused by pneumonitis (n=3), asphyxia, atrial fibrillation, cerebellar hemorrhage, and unspecified death (n=1, each), and two in Arm B caused by pneumonitis and embolism (n=1, each).
Pivotal Phase 2 Trial of Pamiparib in Advanced OC
Poster #820P
“Pamiparib demonstrated strong antitumor activity in patients with advanced ovarian cancer, having achieved clinically meaningful and durable responses in both platinum-sensitive and platinum-resistant patients with BRCA1/2 mutation. This is encouraging news for patients with relapsed disease or patients who discontinued standard treatment due to unacceptable toxicity, and we are excited about pamiparib’s potential to improve treatment outcomes for them,” said
The preliminary results presented at ESMO 2020 were from a Phase 2 dose-expansion portion of a Phase 1/2 trial of pamiparib in patients with advanced ovarian cancer, fallopian cancer, and primary peritoneal cancer or advanced triple negative breast cancer (NCT03333915). A total of 113 patients in
-
In Cohort 1 of patients with PSOC:
- ORR was 64.6% (95% CI: 53.3, 74.9), including eight complete responses (CRs) and 45 partial responses (PRs);
- DCR was 95.1% (95% CI: 88.0, 98.7);
- Cancer antigen (CA)-125 response rate was 79.7% (95% CI: 68.8, 88.2);
- The median DoR was 14.5 months (95% CI: 11.1, not evaluable) and the median PFS was 15.2 months (95% CI: 10.35, not evaluable);
-
In Cohort 2 of patients with PROC:
- ORR was 31.6% (95% CI: 12.6, 56.6), including six PRs;
- DCR was 94.7% (95% CI: 74.0, 99.9);
- CA-125 response rate was 38.1% (95% CI: 18.1, 61.6);
- Pamiparib was generally tolerated, consistent in patients with PSOC and PROC, and similar to other PARP inhibitors;
- Across the trial, the most common (≥20.0%) TEAEs of any grade included anemia (89.4%), nausea (68.1%), decreased neutrophil count (61.1%), decreased white blood cell count (60.2%), vomiting (50.4%), decreased platelet count (31.0%), decreased appetite (30.1%), asthenia (28.3%), diarrhea (22.1%), increased AST (21.2%), decreased lymphocyte count (21.2%), increased ALT (20.4%), and leukopenia (20.4%);
- Across the trial, the most common (≥10.0%) Grade ≥3 TEAEs included anemia (41.6%), decreased neutrophil count (33.6%), decreased white blood cell count (19.5%), and leukopenia (10.6%); and
- No myelodysplastic syndrome or significant complications potentially related to hematologic AEs, such as Grade ≥3 hemorrhage, fever, or infection, were reported in the trial.
To learn more about the data presented at the
About Tislelizumab
Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.
Tislelizumab is approved by the
In addition, three supplemental new drug applications for tislelizumab have been accepted by the
Currently, 16 potentially registration-enabling clinical trials are being conducted in
Tislelizumab is not approved for use outside of
About Pamiparib
Pamiparib (BGB-290) is an investigational inhibitor of PARP1 and PARP2 which has demonstrated pharmacological properties such as brain penetration and PARP-DNA complex trapping in preclinical models. Discovered by
A New Drug Application (NDA) for pamiparib for patients with ovarian cancer has been accepted and granted priority review by CDE of the NMPA.
About
Forward-Looking Statements
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 clinical data from ongoing clinical trials of tislelizumab and pamiparib; the mechanism of action of tislelizumab; the potential for tislelizumab as a treatment for patients with lung cancers and for pamiparib as a treatment for patients with ovarian cancer; and BeiGene’s advancement of, and anticipated clinical development, regulatory milestones, and commercialization of tislelizumab, pamiparib, and its other drug candidates. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including
View source version on businesswire.com: https://www.businesswire.com/news/home/20200917005874/en/
Investor Contact
+1 857-302-5189
ir@beigene.com
Media Contact
+1 857-302-5663 or +1 857-302-7596
media@beigene.com
Source: