BeiGene Provides Update on FDA Advisory Committee Vote on Benefit-Risk Profile of PD-1 Inhibitors, including TEVIMBRA®, for Treatment of ESCC and Gastric/GEJ Cancers
BeiGene (NASDAQ: BGNE) announced that the FDA's Oncologic Drugs Advisory Committee (ODAC) recognizes the favorable benefit-risk profile of PD-1 inhibitors, including TEVIMBRA® (tislelizumab-jsgr), for first-line treatment of advanced esophageal squamous cell carcinoma (ESCC) and gastric/gastroesophageal junction (G/GEJ) cancers with PD-L1 expression >1%. The committee voted to recommend a class-wide PD-L1 expression level cut-off across PD-1 inhibitors for these indications.
The ODAC voted 10-2 (1 abstaining) against using PD-1 inhibitors in G/GEJ with PD-L1 expression <1%, and 11-1 (1 abstaining) against use in ESCC patients with PD-L1 expression <1%. BeiGene's Phase 3 RATIONALE-305 (G/GEJ) and RATIONALE-306 (ESCC) studies met their overall survival endpoints. The Biologics License Applications (BLAs) for TEVIMBRA in these indications are under FDA review.
BeiGene (NASDAQ: BGNE) ha annunciato che il Comitato consultivo sui farmaci oncologici della FDA (ODAC) riconosce il favorevole profilo beneficio-rischio degli inibitori PD-1, inclusi TEVIMBRA® (tislelizumab-jsgr), per il trattamento di prima linea del carcinoma squamoso esofageo avanzato (ESCC) e dei tumori gastrici / giunzione gastroesofagea (G/GEJ) con espressione di PD-L1 >1%. Il comitato ha votato per raccomandare un livello di soglia di espressione di PD-L1 di classe tra gli inibitori PD-1 per queste indicazioni.
L'ODAC ha votato 10-2 (1 astenuto) contro l'uso degli inibitori PD-1 nel G/GEJ con espressione di PD-L1 <1%, e 11-1 (1 astenuto) contro l'uso nei pazienti con ESCC e espressione di PD-L1 <1%. Gli studi di fase 3 RATIONALE-305 (G/GEJ) e RATIONALE-306 (ESCC) di BeiGene hanno raggiunto i loro obiettivi di sopravvivenza globale. Le domande di licenza biologica (BLA) per TEVIMBRA in queste indicazioni sono attualmente in fase di revisione da parte della FDA.
BeiGene (NASDAQ: BGNE) anunció que el Comité Asesor de Medicamentos Oncológicos de la FDA (ODAC) reconoce el favorable perfil de beneficio-riesgo de los inhibidores de PD-1, incluyendo TEVIMBRA® (tislelizumab-jsgr), para el tratamiento de primera línea del carcinoma de células escamosas esofágicas avanzado (ESCC) y de cánceres gástricos / de la unión gastroesofágica (G/GEJ) con expresión de PD-L1 >1%. El comité votó a favor de recomendar un corte de nivel de expresión de PD-L1 de clase para los inhibidores de PD-1 en estas indicaciones.
El ODAC votó 10-2 (1 abstención) en contra del uso de inhibidores de PD-1 en G/GEJ con expresión de PD-L1 <1%, y 11-1 (1 abstención) en contra del uso en pacientes con ESCC y expresión de PD-L1 <1%. Los estudios de Fase 3 RATIONALE-305 (G/GEJ) y RATIONALE-306 (ESCC) de BeiGene cumplieron con sus objetivos de supervivencia global. Las Solicitudes de Licencia Biológica (BLA) para TEVIMBRA en estas indicaciones están bajo revisión de la FDA.
BeiGene (NASDAQ: BGNE)는 FDA의 항암약물 자문위원회(ODAC)가 TEVIMBRA® (tislelizumab-jsgr)를 포함한 PD-1 억제제의 유리한 이익-위험 프로필을 인정한다는 것을 발표했습니다. 이는 진행된 식도 편평세포암(ESCC) 및 위/식도 접합부(G/GEJ) 암의 1차 치료에 대해 PD-L1 발현이 >1%인 경우에 해당합니다. 이 위원회는 이러한 적응증에 대해 PD-1 억제제에 대한 클래스 전반적인 PD-L1 발현 수준 컷오프를 권장하는 투표를 하였습니다.
ODAC는 PD-L1 발현이 <1%인 G/GEJ에서 PD-1 억제제를 사용하는 것에 대해 10-2 (1명 기권)로 반대하였고, ESCC 환자에서 PD-L1 발현이 <1%일 때 사용에 대해서는 11-1 (1명 기권)으로 반대하였습니다. BeiGene의 3상 연구 RATIONALE-305 (G/GEJ)와 RATIONALE-306 (ESCC)은 전체 생존 목표를 달성하였습니다. 이러한 적응증에 대한 TEVIMBRA의 생물학적 면허 신청(BLA)은 FDA의 검토를 받고 있습니다.
BeiGene (NASDAQ: BGNE) a annoncé que le Comité consultatif sur les médicaments oncologiques de la FDA (ODAC) reconnaît le profil bénéfice-risque favorable des inhibiteurs de PD-1, y compris le TEVIMBRA® (tislelizumab-jsgr), pour le traitement de première ligne du carcinome épidermoïde avancé de l'œsophage (ESCC) et des cancers gastriques / de la jonction gastro-œsophagienne (G/GEJ) avec une expression de PD-L1 >1%. Le comité a voté en faveur de recommander un seuil de niveau d'expression de PD-L1 de classe pour ces indications entre les inhibiteurs de PD-1.
L'ODAC a voté 10-2 (1 abstention) contre l'utilisation d'inhibiteurs de PD-1 dans le G/GEJ avec une expression de PD-L1 <1% et 11-1 (1 abstention) contre l'utilisation chez les patients ESCC avec une expression de PD-L1 <1%. Les études de phase 3 RATIONALE-305 (G/GEJ) et RATIONALE-306 (ESCC) de BeiGene ont atteint leurs objectifs de survie globale. Les demandes de licence biologique (BLA) pour TEVIMBRA dans ces indications sont actuellement en cours d'examen par la FDA.
BeiGene (NASDAQ: BGNE) gab bekannt, dass das Onkologische Arzneimittelberatungs-komitee der FDA (ODAC) das günstige Nutzen-Risiko-Profil von PD-1-Inhibitoren, einschließlich TEVIMBRA® (tislelizumab-jsgr), für die Erstlinbehandlung von fortgeschrittenem plattenepithelialen Speiseröhrenkarzinom (ESCC) und Magen-/gastroösophagealen Übergang (G/GEJ) Krebs mit PD-L1-Expression >1% anerkennt. Das Komitee stimmte dafür, einen klassenweiten PD-L1-Expressionslevel-Cut-off für diese Indikationen über PD-1-Inhibitoren zu empfehlen.
Das ODAC stimmte 10-2 (1 Enthaltung) gegen die Verwendung von PD-1-Inhibitoren bei G/GEJ mit PD-L1-Expression <1% und 11-1 (1 Enthaltung) gegen die Verwendung bei ESCC-Patienten mit PD-L1-Expression <1%. Die Phase-3-Studien RATIONALE-305 (G/GEJ) und RATIONALE-306 (ESCC) von BeiGene erfüllten ihre Gesamtüberlebensziele. Die Anträge auf Biologics License Application (BLA) für TEVIMBRA in diesen Indikationen werden derzeit von der FDA geprüft.
- TEVIMBRA showed favorable benefit-risk profile for first-line treatment of ESCC and G/GEJ cancers with PD-L1 expression >1%
- Phase 3 RATIONALE-305 and RATIONALE-306 studies met their overall survival endpoints
- TEVIMBRA's safety profile is consistent with known anti-PD-1 antibodies, with no new safety signals identified
- ODAC voted against using PD-1 inhibitors in G/GEJ and ESCC patients with PD-L1 expression <1%
- Recommended class-wide PD-L1 expression level cut-off may limit the potential patient population for TEVIMBRA
Insights
The FDA Advisory Committee's vote on PD-1 inhibitors, including TEVIMBRA, for ESCC and G/GEJ cancers is a significant development. Key points:
- Recommended PD-L1 expression level cut-off of >1% for treatment
- TEVIMBRA showed statistically significant reduction in death risk in Phase 3 trials
- Safety profile consistent with known anti-PD-1 antibodies
This vote could standardize treatment protocols, potentially narrowing the eligible patient population but also improving treatment efficacy. For BeiGene, while this may limit TEVIMBRA's market size, it could enhance its competitive position within the defined patient group. The ongoing FDA review of TEVIMBRA's BLAs for these indications remains crucial. Investors should monitor how this impacts BeiGene's market position and potential revenue streams in the competitive oncology space.
This FDA advisory committee vote has mixed implications for BeiGene's financial outlook:
- Positive: TEVIMBRA's efficacy in reducing death risk could drive adoption
- Negative: PD-L1 expression cut-off may limit the addressable market
- Neutral: Consistent safety profile doesn't present new concerns or advantages
The standardization of PD-L1 expression criteria across PD-1 inhibitors could level the playing field, potentially benefiting BeiGene if TEVIMBRA shows superior efficacy within the defined patient group. However, it may also intensify competition. The impact on BeiGene's
Vote recommends a class-wide PD-L1 expression level cut-off across PD-1 inhibitors in advanced esophageal squamous cell carcinoma and gastric/gastroesophageal junction cancers
Biologics License Applications for TEVIMBRA in these indications are under review with the FDA
The committee reviewed efficacy and safety data from the Phase 3 RATIONALE-305 (G/GEJ) and RATIONALE-306 (ESCC) studies, as well as other pivotal studies from the two other PD-1 inhibitors approved in these indications. The Advisory Committee voted 10 to 2, with one abstaining, that the risk benefit assessment was not favorable for the use of PD-1 inhibitors in G/GEJ with PD-L1 expression less than
“The survival rates for gastric and esophageal cancer remain strikingly low for the majority of patients who are diagnosed with late-stage disease and there is a need for additional treatments that can extend life,” said Sally Werner, RN, BSN, MSHA, CEO at Cancer Support Community. “We appreciate the FDA's recognition of the need for safe and effective treatments for these cancers. Additional treatment options offer physicians and their patients choices on the treatment that is right for them.”
“The vote by ODAC members to recommend a class-level cut-off of PD-L1 expression for PD-1 inhibitors used in the treatment of gastric/GEJ cancers and ESCC will help to establish a standard for clinicians and the patients they treat,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “We look forward to working with the FDA as it completes its review of our BLAs for TEVIMBRA, and we strive to bring this therapy to applicable patients in the U.S.”
Both the RATIONALE-305 and RATIONALE-306 studies met their endpoints of overall survival (OS), demonstrating a statistically significant reduction in the risk of death across both indications. The safety profile for TEVIMBRA in combination with chemotherapy is consistent with the known safety profile of anti-PD-1 antibodies, and no new safety signals were identified.
The Biologics License Applications (BLAs) for TEVIMBRA in these indications remain under review with the FDA. TEVIMBRA is currently approved in the
About RATIONALE-305
RATIONALE-305 (NCT03777657) is a randomized, double-blind, placebo-controlled, global Phase 3 that enrolled 997 patients with advanced unresectable or metastatic G/GEJ adenocarcinoma. The primary endpoint was OS, with prespecified hierarchy testing for the PD-L1 high population followed by the intent-to-treat (ITT) population. Results of the final analysis of the ITT population were presented as a late-breaking oral presentation during the European Society for Medical Oncology (ESMO) Congress 2023.
About RATIONALE-306
RATIONALE-306 (NCT03783442) is a randomized, placebo-controlled, double-blind, global Phase 3 study to evaluate the efficacy and safety of tislelizumab in combination with chemotherapy as a first-line treatment in patients with advanced or metastatic ESCC. The primary endpoint of the trial is overall survival. Secondary endpoints include progression free survival, overall response rate, and duration of response per RECIST v1.1, as well as health-related quality of life measures and safety. The trial enrolled 649 patients at research centers across
About TEVIMBRA® (tislelizumab-jsgr)
Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.
INDICATION
TEVIMBRA (tislelizumab-jsgr), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.
WARNINGS AND PRECAUTIONS
Severe and Fatal Immune-Mediated Adverse Reactions
TEVIMBRA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated reactions.
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue TEVIMBRA depending on severity. In general, if TEVIMBRA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.
Immune-Mediated Pneumonitis
TEVIMBRA can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.
Immune-mediated pneumonitis occurred in
Systemic corticosteroids were required in all patients with pneumonitis. Immune-mediated pneumonitis resolved in
Immune-Mediated Colitis
TEVIMBRA can cause immune-mediated colitis, which can be fatal. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.
Immune-mediated colitis occurred in
Immune-Mediated Hepatitis
TEVIMBRA can cause immune-mediated hepatitis, which can be fatal.
Immune-mediated hepatitis occurred in
Immune-Mediated Endocrinopathies
Adrenal Insufficiency
TEVIMBRA can cause immune-mediated adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold TEVIMBRA depending on severity.
Immune-mediated adrenal insufficiency occurred in
Hypophysitis
TEVIMBRA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity.
Hypophysitis/hypopituitarism occurred in
Thyroid Disorders
TEVIMBRA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity.
Thyroiditis: Immune-mediated thyroiditis occurred in
Hyperthyroidism: Immune-mediated hyperthyroidism occurred in
Hypothyroidism: Immune-mediated hypothyroidism occurred in
Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis
Type 1 diabetes mellitus has been reported with PD-1/PD-L1 blocking antibodies. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity.
Immune-Mediated Nephritis with Renal Dysfunction
TEVIMBRA can cause immune-mediated nephritis, which can be fatal.
Immune-mediated nephritis with renal dysfunction occurred in
Immune-Mediated Dermatologic Adverse Reactions
TEVIMBRA can cause immune-mediated rash or dermatitis. Cases of severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported, some with fatal outcome. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue TEVIMBRA depending on severity.
Immune-mediated dermatologic adverse reactions occurred in
Other Immune-Mediated Adverse Reactions
The following clinically significant immune-mediated adverse reactions occurred at an incidence of less than
The following additional clinically significant immune-mediated adverse reactions have been reported with other PD-1/PD-L1 blocking antibodies, including severe or fatal cases.
Cardiac/Vascular: Vasculitis
Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy.
Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis
Musculoskeletal and Connective Tissue: Polymyositis, rhabdomyolysis and associated sequelae including renal failure
Endocrine: Hypoparathyroidism
Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.
Infusion-Related Reactions
TEVIMBRA can cause severe or life-threatening infusion-related reactions. Infusion-related reactions occurred in
Slow the rate of infusion for mild (Grade 1) and interrupt the infusion for moderate (Grade 2) infusion-related reactions. For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue TEVIMBRA.
Complications of Allogeneic HSCT
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.
Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on its mechanism of action, TEVIMBRA can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TEVIMBRA and for 4 months after the last dose.
ADVERSE REACTIONS
Permanent discontinuation of TEVIMBRA due to an adverse reaction occurred in
Dosage interruptions of TEVIMBRA due to an adverse reaction occurred in
The most common (≥
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About BeiGene
BeiGene is a global oncology company that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn, X (formerly known as Twitter), Facebook and Instagram.
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 BeiGene’s ability to bring TEVIMBRA to additional patients in the
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FAQ
What did the FDA Advisory Committee vote on regarding TEVIMBRA (BGNE) for ESCC and G/GEJ cancers?
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How did the FDA Advisory Committee vote on PD-1 inhibitors for patients with low PD-L1 expression in ESCC and G/GEJ cancers?
