Gilead’s Phase 2 EVOKE-02 Study of Trodelvy® (sacituzumab govitecan-hziy) in Combination With KEYTRUDA® (pembrolizumab) Demonstrates Promising Clinical Activity in First-Line Metastatic Non-Small Cell Lung Cancer
- Encouraging activity of Trodelvy in combination with KEYTRUDA in 1L metastatic NSCLC
- Positive response rates and duration of response compared to historical responses to anti-PD1 monotherapy
- Support for further investigation of sacituzumab govitecan as a potential IO-combination option in first-line metastatic NSCLC
- None.
– Results Show Encouraging Activity of Trodelvy in Combination with KEYTRUDA in 1L Metastatic NSCLC Across all PD-L1 Subgroups and Histologies Studied –
– Results Support Further Investigation of Trodelvy in Combination with KEYTRUDA in 1L Metastatic NSCLC–
The preliminary analysis of the EVOKE-02 study includes results of two cohorts: Trodelvy in combination with KEYTRUDA in first-line advanced or metastatic squamous/non-squamous NSCLC with PD-L1 tumor proportion score (TPS) ≥
“Patients with metastatic NSCLC continue to need novel treatment options. The data from the EVOKE-02 study gives us confidence in the clinical activity of sacituzumab govitecan in combination with pembrolizumab in first-line metastatic NSCLC patients,” said Byoung Chul Cho, MD, PhD, Professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine. “The positive response rates and duration of response across patients treated with the combination shows promise compared with historical responses to anti-PD1 monotherapy in this setting. These data support further investigation of sacituzumab govitecan as a potential IO-combination option in first-line metastatic NSCLC.”
“The EVOKE-02 trial is the first data presented from several Gilead studies dedicated to exploring Trodelvy’s potential in lung cancer,” said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology. “These data are very encouraging and confirms our approach for the ongoing Phase 3 EVOKE-03 study of Trodelvy in combination with KEYTRUDA vs. KEYTRUDA monotherapy for patients in first-line PD-L1-high metastatic NSCLC. We look forward to potentially bringing a new treatment option to previously untreated metastatic NSCLC patients.”
The safety profile of Trodelvy in combination with KEYTRUDA in the EVOKE-02 study was consistent with the known safety of each agent. The most common any-grade TEAEs were diarrhea (
Gilead entered into two clinical trial collaboration and supply agreements with Merck (known as MSD outside of
The use of Trodelvy for the treatment of NSCLC and the use of Trodelvy in combination with KEYTRUDA for any use is investigational, and the safety and efficacy for these uses have not been established or approved by any regulatory agency globally. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.
About Metastatic Non-Small Cell Lung Cancer
Worldwide, more than two million people were diagnosed with lung cancer in 2020. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for up to
About the EVOKE-02 Study
The EVOKE-02 study is an open-label, global, multi-center, multi-cohort, Phase 2 study evaluating Trodelvy in combination with KEYTRUDA with or without chemotherapy regardless of PD-L1 expression in patients with advanced or metastatic NSCLC without actionable genomic alterations. Patients were assigned to cohorts according to disease status or PD-L1 expression. Patients were assigned to Cohorts A or B according to Tumor Proportion Score (TPS) status:
-
Cohort A enrolled patients with squamous/non-squamous NSCLC with TPS ≥
50% . -
Cohort B enrolled patients with squamous/non-squamous NSCLC with TPS <
50% .
Patients enrolled in Cohorts A or B received the combination of Trodelvy and KEYTRUDA.
Following enrolment in a safety run-in cohort, patients will be enrolled in Cohorts C or D according to disease status for carboplatin combinations.
- Cohort C enrolled patients with non-squamous NSCLC with any PD-L1 expression level.
- Cohort D enrolled patients with squamous NSCLC with any PD-L1 expression level.
Patients enrolled in Cohorts C or D received Trodelvy plus KEYTRUDA plus platinum agent.
The primary endpoints are objective response rate (ORR) as assessed by independent review per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and percentage of participants experiencing dose-limiting toxicities (DLTs) per dose level in the safety run-in cohorts. Additional efficacy measures include progression-free survival (PFS), overall survival (OS), duration of response (DoR) and disease control rate (DCR). More information about EVOKE-02 is available at https://clinicaltrials.gov/study/NCT05186974.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,
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
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 in the
Trodelvy is also being developed 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), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.
In
- 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.
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
Diarrhea: Diarrhea occurred in
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
Nausea and Vomiting: Nausea occurred in
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
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 (≥
In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥
In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥
In the TROPHY study (locally advanced or metastatic urothelial cancer), the most common adverse reactions (incidence ≥
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 Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in
Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving Trodelvy; uncertainties relating to regulatory applications for Trodelvy and related filing and approval timelines, including with respect pending or potential applications for the treatment of metastatic TNBC, HR+/HER2- metastatic breast cancer, metastatic UC, metastatic NSCLC, metastatic SCLC, head and neck cancer, and endometrial cancer, in the currently anticipated timelines or at all; Gilead’s ability to receive regulatory approvals for such indications in a timely manner or at all, and the risk that any such approvals may be subject to significant limitations on use; the possibility that Gilead may make a strategic decision to discontinue development of Trodelvy for such indications and as a result, Trodelvy may never be commercialized for these indications; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, as filed with the
Trodelvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.
For more information about Gilead, please visit the company’s website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
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Source: Gilead Sciences, Inc.