Gilead and Kite Oncology to Highlight Broad and Diverse Oncology Portfolio at ASCO 2024
– Non-Small Cell Lung Cancer Development Program Data to be Presented, Including the Phase 3 EVOKE-01 Study –
– Updated Results from Phase 2 EDGE-Gastric Study of Fc-Silent Anti-TIGIT Domvanalimab Plus Anti-PD-1 Zimberelimab, to be Presented –
– Pilot Study Results of Yescarta® in Relapsed/Refractory Primary and Secondary Central Nervous System Lymphomas, an Area of Unmet Clinical Need, to be Presented Orally –
FOSTER CITY, Calif. & SANTA MONICA, Calif.–(BUSINESS WIRE)–Gilead Sciences, Inc. (Nasdaq: GILD) and Kite, a Gilead Company, will present 18 abstracts during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. These data showcase the ongoing commitment to developing differentiated approaches to transform how cancer is treated and span solid tumors and blood cancers, including lung, breast, gastrointestinal, colorectal, leukemia and lymphoma.
New Data Provide Detail on Trodelvy in Non-Small Cell Lung Cancer (NSCLC)
Gilead is presenting primary results from the global Phase 3 EVOKE-01 study of Trodelvy® (sacituzumab govitecan-hziy) versus docetaxel in patients with advanced or metastatic NSCLC that has progressed on or after platinum-based chemotherapy and checkpoint inhibitor therapy. In addition, Gilead will present longer-term results from Cohort A of the Phase 2 EVOKE-02 study of Trodelvy in combination with KEYTRUDA® (pembrolizumab) in first-line advanced or metastatic squamous/non-squamous PD-L1-high NSCLC.
Gilead Highlights Progress in Gastrointestinal Pipeline
An updated analysis from the Phase 2 EDGE-Gastric study will be featured as a rapid oral presentation in partnership with Arcus Biosciences. These longer-term efficacy and safety results for domvanalimab, an Fc-silent anti-TIGIT antibody, plus the anti-PD-1 antibody zimberelimab and chemotherapy, as a potential first-line treatment for upper gastrointestinal cancers follow the encouraging ORR and six-month PFS rate results from the preliminary analysis presented during the November 2023 virtual ASCO Plenary Series.
Additionally, an oral presentation with our partner Arcus Biosciences will feature data from Cohort B of ARC-9, a Phase 1b/2 study evaluating the safety and efficacy of etrumadenant, a dual A2a/b adenosine receptor antagonist, plus zimberelimab, and FOLFOX/bevacizumab in third-line metastatic colorectal cancer (mCRC).
Kite Showcases New Data on CAR T-cell Therapies
A pilot collaborative study evaluating Yescarta® (axicabtagene ciloleucel) for the treatment of patients with relapsed/refractory (R/R) primary and secondary central nervous system lymphoma (PCNSL and SCNSL) will be presented orally. These updated data will highlight the efficacy and safety of Yescarta in this patient population with important unmet need.
Additionally, updated overall survival outcomes for Tecartus® (brexucabtagene autoleucel) from the pivotal Phase 1/2 ZUMA-3 trial, now with more than four years of follow-up, will be presented. The ZUMA-3 trial is the longest follow-up in an adult-only study of a CAR T-cell therapy for R/R B-cell lymphoblastic leukemia (B-ALL). These data continue to support the long-term survival and durability of Tecartus.
Summary of Presentations
Accepted abstracts at the 2024 ASCO Annual Meeting include:
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Tumor Types |
Abstract Title |
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B-cell Acute Lymphoblastic Leukemia |
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Abstract #6531 June 3, 2024 9:00 AM – 12:00 PM CDT (Poster) |
Long-term Survival Outcomes of Patients (pts) with Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia (R/R B-ALL) Treated with Brexucabtagene Autoleucel (brexu-cel) in ZUMA-3
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Biliary Tract Cancer |
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Abstract #TPS4195 June 1, 2024 1:30 – 4:30 PM CDT (TiP) |
Phase 2 Study of Gemcitabine, Cisplatin, Quemliclustat (AB680) and Zimberelimab (AB122) During First-Line Treatment of Advanced Biliary Tract Cancers (BTC) – Big Ten Cancer Research Consortium Study BTCRC-GI22-564 |
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Breast Cancer |
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Abstract #LBA1004 June 1, 2024 3:00-6:00 PM CDT (Oral Presentation) |
SACI-IO HR+: A Randomized Phase II Trial of Sacituzumab Govitecan with or without Pembrolizumab in Patients with Metastatic Hormone Receptor-positive/HER2-negative Breast Cancer* |
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Abstract #1101 June 2, 2024 9:00 AM – 12:00 PM CDT (Poster) |
Prevention of Sacituzumab Govitecan (SG)-related Neutropenia and Diarrhea in Patients (pts) with Triple-negative or HR+/HER2- Advanced Breast Cancer (ABC) (PRIMED): a Phase 2 Trial** |
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Abstract #1075 June 2, 2024 9:00 AM – 12:00 PM CDT (Poster) |
Genomic Alterations in DNA Damage Response (DDR) Genes in HR+/HER2- Metastatic Breast Cancer (mBC) and Impact on Clinical Efficacy with Sacituzumab Govitecan (SG): Biomarker Results from TROPiCS-02 Study |
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Abstract #1102 June 2, 2024 9:00 AM – 12 PM CDT (Poster) |
Sequential Combination of Sacituzumab Govitecan and PARP Inhibitor Talazoparib in Metastatic Triple Negative Breast Cancer (mTNBC): Results from the Phase II Study |
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Abstract #TPS1140 June 2, 2024 9:00 AM – 12 PM CDT (TiP) |
Trial in Progress: Phase I/II Study of Stereotactic Radiation and Sacituzumab Govitecan with Zimberelimab in the Management of Metastatic Triple Negative Breast Cancer with Brain Metastases |
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Central Nervous System Lymphoma |
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Abstract #2006 June 3, 2024 8:00 – 11:00 AM CDT (Oral Presentation) |
A Pilot Study of Axicabtagene Ciloleucel (axi-cel) for the Treatment of Relapsed/Refractory Primary and Secondary Central Nervous System Lymphoma (PCNSL and SCNSL)*
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Colorectal Cancer |
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Abstract #3508 June 2, 2024 8:00 – 11:00 AM CDT (Oral Presentation) |
Randomized Phase 1b/2 Study to Evaluate Etrumadenant Based Treatment Combinations in Previously Treated Metastatic Colorectal Cancer (mCRC) |
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Gastroesophageal Cancers |
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Abstract #433248 June 1, 2024 12:30 – 1:30 PM CDT (Oral Presentation) |
EDGE-Gastric Arm A1: Phase 2 Study of Domvanalimab, Zimberelimab, and FOLFOX in First-Line Advanced Gastroesophageal Cancer |
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Lung Cancer |
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Abstract #LBA8500 May 31, 2024 2:45 – 5:45 PM CDT (Oral Presentation) |
Sacituzumab Govitecan (SG) vs Docetaxel (doc) in Patients (pts) with Metastatic Non-small Cell Lung Cancer (mNSCLC) Previously Treated with Platinum (PT)-based Chemotherapy (chemo) and PD(L)-1Inhibitors (IO): Primary Results from the Phase 3 EVOKE-01 Study |
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Abstract #8592 June 3, 2024 1:30 – 4:30 PM CDT (Poster) |
Sacituzumab Govitecan (SG) + Pembrolizumab (pembro) in First-line (1L) Metastatic Non-small Cell Lung Cancer (mNSCLC): Results from Longer Follow-up of Cohort A of EVOKE-02 |
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Abstract #TPS8121 June 3, 2024 1:30 – 4:30 PM CDT (TiP) |
VELOCITY-Lung Substudy-03: a Phase 2 Study Evaluating Safety and Efficacy of Domvanalimab (Dom) + Zimberelimab (Zim) or Zim Alone in Combination with Chemotherapy (Chemo) in the Neoadjuvant Phase and Dom+Zim or Zim Alone in the Adjuvant Phase in Patients with Resectable Stage II-III Non-small Cell Lung Cancer (NSCLC) |
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Rare Genitourinary Tumors |
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Abstract #TPS4627 June 2, 2024 9:00 AM – 12 PM CDT (TiP) |
SMART: A Phase II Study of Sacituzumab Govitecan (SG) with or without Atezolizumab Immunotherapy in Rare Genitourinary (GU) Tumors such as Small Cell, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma (RMC) and Penile Cancer* |
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Solid Tumors |
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Abstract #3029 June 1, 2024 9:00 AM – 12:00 PM CDT (Poster) |
Pooled Safety Analysis of Sacituzumab Govitecan (SG) in Multiple Solid Tumor Types |
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Thyroid Cancer |
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Abstract #TPS6130 June 2, 2024 9:00 AM – 12:00 PM CDT (TiP) |
Sacituzumab Govitecan in Patients with Advanced or Metastatic Radioactive-iodine Refractory Thyroid Carcinoma: The Phase 2 SETHY, GETNE-T2318 Trial |
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Urothelial Cancer |
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Abstract #e16500 May 23, 2024 4:00 PM CDT (Online Publication Only) |
Treatment Patterns of Metastatic Urothelial Cancer in the United States |
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Abstract #TPS4618 June 2, 2024 9:00 AM – 12:00 PM CDT (TiP) |
Sacituzumab Govitecan (SG) plus Enfortumab Vedotin (EV) for Metastatic Urothelial Carcinoma (mUC) Treatment Experienced (DAD) and with Pembrolizumab (P) in Treatment Naïve UC (DAD-IO)** |
*Collaborative study with Dana-Farber Cancer Institute
**Collaborative study
Domvanalimab, zimberelimab and etrumadenant are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use of these molecules, and their safety and efficacy for the treatment of gastrointestinal and lung cancers have not been established.
Trodelvy has not been approved by any regulatory agency for the treatment of metastatic NSCLC. Its safety and efficacy have not been established for this indication. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for the approved U.S. Indication and additional Important Safety Information.
About Trodelvy
Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast, bladder and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.
Trodelvy is approved in almost 50 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Trodelvy is also approved to treat certain patients with pre-treated HR+/HER2- metastatic breast cancer in Australia, Brazil, Canada, the European Union, Israel, United Arab Emirates and the United States. In the U.S., Trodelvy has an accelerated approval for treatment of certain patients with second-line metastatic urothelial cancer; see below for full indication statements.
Trodelvy is being explored for potential investigational use in other TNBC, HR+/HER2- and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including metastatic non-small cell lung cancer (NSCLC), head and neck cancer, gynecological cancer, and gastrointestinal cancers.
U.S. Indications for Trodelvy
In the United States, Trodelvy is indicated for the treatment of adult patients with:
- Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
- Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
- Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
U.S. Important Safety Information for Trodelvy
BOXED WARNING: NEUTROPENIA AND DIARRHEA
- Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
- Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS
- Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS
Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 64% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever. Administer G-CSF as clinically indicated or indicated in Table 1 of USPI.
Diarrhea: Diarrhea occurred in 64% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.
Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.
Nausea and Vomiting: Nausea occurred in 64% of all patients treated with Trodelvy and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.
Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.
Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.
ADVERSE REACTIONS
In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).
In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.
In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.
In the TROPHY study (locally advanced or metastatic urothelial cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, any infection, alopecia, decreased appetite, constipation, vomiting, rash, and abdominal pain. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.
DRUG INTERACTIONS
UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.
UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.
Please see full Prescribing Information, including BOXED WARNING.
About Tecartus
Please see full FDA Prescribing Information, including BOXED WARNING and Medication Guide.
Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
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Adult patients with relapsed or refractory mantle cell lymphoma (MCL).
This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. - Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
U.S. IMPORTANT SAFETY INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES
- Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving Tecartus. Do not administer Tecartus to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
- Neurologic toxicities, including life-threatening reactions, occurred in patients receiving Tecartus, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Tecartus. Provide supportive care and/or corticosteroids as needed.
- T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies.
- Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.
Ensure that a minimum of two doses of tocilizumab are available for each patient prior to infusion of Tecartus. Following infusion, monitor patients for signs and symptoms of CRS daily for at least seven days at the certified healthcare facility, and for four weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.
Neurologic Events, including those that were fatal or life-threatening, occurred following treatment with Tecartus. Neurologic events occurred in 87% (68/78) of patients with ALL, including ≥ Grade 3 in 35% of patients. The median time to onset for neurologic events was seven days (range: 1 to 51 days) with a median duration of 15 days (range: 1 to 397 days) in patients with ALL. For patients with MCL, 54 (66%) patients experienced CRS before the onset of neurological events. Five (6%) patients did not experience CRS with neurologic events and eight patients (10%) developed neurological events after the resolution of CRS. Neurologic events resolved for 119 out of 134 (89%) patients treated with Tecartus. Nine patients (three patients with MCL and six patients with ALL) had ongoing neurologic events at the time of death. For patients with ALL, neurologic events occurred before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients; respectively. Three patients (4%) had neurologic events without CRS. The onset of neurologic events can be concurrent with CRS, following resolution of CRS or in the absence of CRS.
The most common neurologic events (>10%) were similar in MCL and ALL and included encephalopathy (57%), headache (37%), tremor (34%), confusional state (26%), aphasia (23%), delirium (17%), dizziness (15%), anxiety (14%), and agitation (12%).
Contacts
Jacquie Ross, Investors
[email protected]
Meaghan Smith, Media
[email protected]
Anna Padula, Kite Media
[email protected]