Gilead Provides Update On Phase 3 EVOKE-01 Study

On January 22, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) reported that the Phase 3 EVOKE-01 study did not meet its primary endpoint of overall survival (OS) in previously treated metastatic non-small cell lung cancer (NSCLC) (Press release, Gilead Sciences, JAN 22, 2024, View Source [SID1234639412]). EVOKE-01 is evaluating Trodelvy (sacituzumab govitecan-hziy; SG) vs. docetaxel in patients with metastatic or advanced NSCLC that had progressed on or after platinum-based chemotherapy and checkpoint inhibitor therapy.

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A numerical improvement in OS favoring SG was observed in the study, including in patients with both squamous and non-squamous histology. The safety profile for Trodelvy was consistent with prior studies. Trodelvy was generally well tolerated, and no new safety signals were identified in this patient population.

A more than three-month difference in median OS favoring SG was observed in a sub-group of patients non-responsive to last prior anti-PD-(L)1 therapy, representing over 60% of the trial population. This analysis was pre-specified in the protocol, but not alpha-controlled for formal statistical testing. This magnitude of difference was not observed in the sub-group of patients with response to last prior anti-PD-(L)1 therapy. Gilead intends to explore potential pathways to further understand the role SG may have in these patients given the high unmet medical need.

Gilead plans to discuss results from this trial with regulators. The data will be presented at an upcoming medical meeting.

"The totality of our data gives us continued confidence in Trodelvy’s potential in metastatic NSCLC, and in our broader lung cancer clinical development program," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "Treating metastatic NSCLC that has progressed on or after platinum-based chemotherapy presents significant challenges and the need for safe and effective treatments remains urgent. We will work to further identify the metastatic NSCLC patient populations that may benefit from Trodelvy."

Gilead’s clinical development program in metastatic NSCLC is broad and includes multiple ongoing registrational Phase 3 studies and several ongoing Phase 2 studies. Based on strong preliminary efficacy and safety data from the Phase 2 EVOKE-02 study of Trodelvy in combination with pembrolizumab, presented at the World Conference on Lung Cancer 2023, Gilead remains confident in its ongoing Phase 3 EVOKE-03 study in 1L metastatic PD-L1 high NSCLC. The EVOKE-03 study is currently enrolling. In addition, Gilead has a broad clinical development program in lung cancer with domvanalimab, the first Fc-silent investigational anti-TIGIT antibody.

Despite recent advances with multiple immunotherapy treatment options for first-line metastatic NSCLC, most people’s cancer will eventually progress. Only about 35-55% of patients respond to immunotherapy-based combinations in the frontline setting, and after progression there are limited treatment options available, particularly for those who did not have a response to immunotherapy. Developing novel options for patients who have progressed on platinum-based chemotherapy and checkpoint inhibitor therapy is a challenge with limited treatment advancements made for these patients.

Gilead would like to thank the patients, families, investigators, and advocates who contributed to this important research.

Trodelvy is the first approved Trop-2-directed antibody-drug conjugate (ADC) that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers and improved clinical outcomes for certain people with 2L metastatic urothelial cancer.

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 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 85% of diagnoses. About half of NSCLC cases are diagnosed at the metastatic stage (57%), when treatment is especially difficult. Even in patients whose disease is caught early, half will eventually progress to the metastatic stage within five years. Newly diagnosed patients have several treatment options including platinum-based therapy, checkpoint inhibitors and targeted therapies. However, there are limited treatment options once patients with metastatic NSCLC progress on or after platinum-based chemotherapy and checkpoint inhibitors.

About the EVOKE-01 Study

The EVOKE-01 study is a global, multi-center, open-label Phase 3 study randomized 1:1 to evaluate Trodelvy vs. docetaxel in patients with advanced or metastatic NSCLC that has progressed on or after platinum-based chemotherapy and checkpoint inhibitor therapy. The study enrolled 603 participants. The primary endpoint is overall survival (OS). Key secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and disease control rate (DCR) as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and safety. Additional efficacy measures include time to first deterioration in shortness of breath domain as measured by NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) Score and time to first deterioration NSCLC-SAQ Total Score. Further study details are available on clinicaltrials.gov (NCT05089734).

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.

Haystack Oncology, developer of Haystack MRD™, and TriSalus Life Sciences collaborate in connection with the clinical development of TriSalus’ TLR9 agonist in hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and pancreatic adenocarcinoma

On January 22, 2024 Haystack Oncology, a Quest Diagnostics (NYSE: DGX) company and developer of best-in-class personalized MRD technology (Haystack MRD), reported that it has entered a research collaboration with TriSalus Life Sciences to evaluate therapeutic response and provide molecular insights in connection with the clinical development of TriSalus’ SD-101, an investigational class C toll-like receptor-9 (TLR9) agonist (Press release, Quest Diagnostics, JAN 22, 2024, View Source,-developer-of-Haystack-MRD-TM-,-and-TriSalus-Life-Sciences-collaborate-in-connection-with-the-clinical-development-of-TriSalus-TLR9-agonist-in-hepatocellular-carcinoma,-intrahepatic-cholangiocarcinoma,-and-pancreatic-adenocarc [SID1234639410]). SD-101 is delivered via hepatic arterial infusion or pancreatic retrograde venous infusion in their phase 1 and 1b clinical trials using their proprietary Pressure-Enabled Drug Delivery (PEDD) to overcome the challenges associated with intratumoral pressure for patients diagnosed with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and pancreatic adenocarcinoma.

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"Haystack MRD is specifically designed and developed to accurately detect circulating tumor DNA (ctDNA) with unparalleled sensitivity in patients with low tumor burden and in clinically challenging cancer types," said Dan Edelstein, Vice President and General Manager, Haystack Oncology. "Haystack MRD’s sensitivity enables clinical investigators to closely follow molecular response and measure early evidence of treatment efficacy. We’re excited to collaborate with TriSalus to support the clinical development of SD-101 in combination with their unique therapy delivery technology, which aims to overcome challenges associated with treating liver and pancreatic tumors."

Hepatocellular carcinoma is the most common form of liver cancer. Intrahepatic cholangiocarcinoma is cancer that occurs in the parts of the bile ducts that are within the liver. Pancreatic adenocarcinoma is the most common form of pancreatic cancer.

"A significant challenge in the development of immunotherapies for liver and pancreatic tumors is early measurement of response to treatment. Conventional imaging response assessment methods may be misleading in certain situations, and accurate ctDNA assays offer the potential to identify meaningful biologic activity in difficult to treat cancers," says Steven Katz, MD, Chief Medical Officer of TriSalus Life Sciences. "We are thrilled to work with Haystack in pursuit of our mission to develop better therapeutic options for patients with liver and pancreatic tumors."

ORIC Pharmaceuticals Announces $125 Million Private Placement Financing

On January 22, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that it has agreed to sell approximately 12.5 million shares of its common stock to a select group of institutional and accredited healthcare specialist investors in a private placement, at a price per share of $10.00, representing a premium of approximately 10% to ORIC’s 5-day trailing average price (Press release, ORIC Pharmaceuticals, JAN 22, 2024, View Source [SID1234639409]). The financing is expected to close on January 23, 2024, subject to customary closing conditions. ORIC anticipates the gross proceeds from the private placement to be approximately $125 million, before deducting any offering related expenses.

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The financing includes participation from new and existing institutional investors, including Viking Global Investors, Commodore Capital, Frazier Life Sciences, Venrock Healthcare Capital Partners, NEA, and Nextech1.

ORIC intends to use the net proceeds from the proposed financing to fund research and development of its clinical-stage product candidates and research programs and for working capital and general corporate purposes. The proceeds from this financing, combined with current cash, cash equivalents and marketable securities, is expected to be sufficient to fund the current operating plan into late 2026.

The securities described above have not been registered under the Securities Act of 1933, as amended. Accordingly, these securities may not be offered or sold in the United States, except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act. ORIC has agreed to file a registration statement with the U.S. Securities and Exchange Commission (the "SEC") registering the resale of the shares of common stock issued in this private placement. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

Dianthus Therapeutics Announces $230 Million Private Placement

On January 22, 2024 Dianthus Therapeutics, Inc. ("Dianthus" or the "Company") (NASDAQ: DNTH), a clinical-stage biotechnology company dedicated to advancing the next generation of antibody complement therapeutics to treat severe autoimmune diseases, reported that it has entered into a securities purchase agreement for a private investment in public equity ("PIPE") financing that is expected to result in gross proceeds of approximately $230 million to the Company, before deducting placement agent fees and offering expenses (Press release, Magenta Therapeutics, JAN 22, 2024, View Source [SID1234639408]). The PIPE financing included participation from both new and existing investors, including Bain Capital Life Sciences, RA Capital Management, Avidity Partners, Fairmount, Venrock Healthcare Capital Partners, RTW Investments, Great Point Partners LLC, Octagon Capital, Janus Henderson Investors, Vestal Point Capital, Logos Capital, Catalio Capital Management, Woodline Partners LP, Ally Bridge Group, Tellus BioVentures, StemPoint Capital LP and a large investment management firm.

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Pursuant to the terms of the securities purchase agreement, Dianthus is selling an aggregate of 14,500,500 shares of its common stock at a price of $12.00 per share and, in lieu of common stock to certain investors, pre-funded warrants to purchase up to 4,666,332 shares of common stock at a purchase price of $11.999 per pre-funded warrant, which represents the per share purchase price for the common stock less the $0.001 per share exercise price for each pre-funded warrant. The PIPE financing is expected to close on or about January 24, 2024, subject to satisfaction of customary closing conditions.

The Company intends to use the net proceeds from the PIPE financing, together with the Company’s existing cash, cash equivalents, and marketable securities, for research and development expenditures focused on product development and for general corporate purposes, including capital expenditures, working capital and potential business development activities.

Jefferies, Evercore ISI, Stifel, Guggenheim Securities, and Raymond James are acting as placement agents for the PIPE financing.

The offer and sale of the foregoing securities are being made in a transaction not involving a public offering and the securities have not been registered under the Securities Act of 1933, as amended, and may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements. Concurrently with the execution of the securities purchase agreement, Dianthus and the investors entered into a registration rights agreement pursuant to which the Company has agreed to file a registration statement with the Securities and Exchange Commission (the "SEC") registering the resale of the shares of common stock sold in the PIPE financing, as well as the shares of common stock underlying the pre-funded warrants sold in the PIPE financing.

Latest Phase III trial data investigating Cabometyx® in combination with immunotherapy to be presented at ASCO GU 2024

On January 22, 2024 Ipsen (Euronext: IPN; ADR: IPSEY) reported new data to be presented for Cabometyx (cabozantinib) in combination with immunotherapy across indications at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Symposium (ASCO GU) taking place on 25-27 January 2024 in San Francisco, U.S (Press release, Ipsen, JAN 22, 2024, View Source [SID1234639407]).

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Detailed top-line results from the Phase III CONTACT-02 trial of the combination of Cabometyx and atezolizumab versus a second novel hormone therapy (NHT) in people living with metastatic castration-resistant prostate cancer (mCRPC) and measurable extra-pelvic soft tissue disease who have progressed on one prior NHT, are to be presented as an oral presentation (Abstract #18).

With a median follow-up of 14.3 months, data from the primary analysis of progression-free survival (PFS) from the CONTACT-02 trial demonstrated a statistically significant PFS benefit for the combination of Cabometyx and atezolizumab of 6.3 months versus 4.2 months for a second NHT (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.50-0.84; p=0.0007). At an interim analysis for the other primary endpoint of overall survival (OS), the data demonstrated a trend toward improvement for the combination, however, these data were immature, and the trial will continue to the next planned analysis, anticipated in 2024. Safety for the combination appeared to be consistent with the known safety profiles of the individual medicines, and no new safety signals were identified.

Prostate cancer is the second most common cancer in men1 and for those living with advanced metastatic castration-resistant disease, the prognosis is poor, with an estimated survival of 1-2 years2.

"At the advanced metastatic castration-resistant stage of disease, the prognosis is poor, with a median survival of two years and limited available treatment options," said Stéphane Oudard, Professor of Oncology and Chief of the Oncology Clinical and Translational Research Unit at Georges Pompidou Hospital in Paris, France. "These results from the CONTACT-02 trial represent a positive step in the context of the current treatment landscape, contributing the first positive Phase III data of its kind for the benefit of patients, as we await further data from the overall survival analysis."

Also, four-year extended follow-up data from the landmark Phase III CheckMate -9ER trial investigating the combination of Cabometyx and nivolumab versus sunitinib in people living with previously untreated advanced renal cell carcinoma (aRCC) will be presented (Abstract #362).

With a median follow-up of 55.6 months for OS, the combination of Cabometyx and nivolumab demonstrated a sustained and clinically meaningful OS benefit versus sunitinib, with an absolute median OS gain of 10.5 months (46.5 months for the combination vs 36.0 months for sunitinib, HR 0.77, 95% CI: 0.63-0.95). Additionally, median PFS remained almost double that for the combination versus sunitinib, at 16.4 vs 8.4 months respectively (HR 0.58, 95% CI: 0.49-0.70). The safety profile was consistent with the known safety profiles of the individual medicines, and no new safety signals were identified.

Renal cell carcinoma is the most common form of kidney cancer3, 4 and for the 30% of people diagnosed with an advanced form of the disease, the 5-year survival rate is low at 12%, with no identified cure for this disease.5,6

"Data from our ongoing trials continue to reinforce the value of Cabometyx for patients across a number of challenging tumor types," said Christelle Huguet, EVP and Head of Research and Development, Ipsen. "In combination with immunotherapy, Cabometyx is delivering long-term survival benefits today for people living with renal cell carcinoma worldwide, while also showcasing future potential in metastatic castration-resistant prostate cancer, an area of significant unmet need where no other trials of this modality have proven successful in recent decades."

Additionally, health-related quality of life (HRQoL) data from a modelling analysis based on the CheckMate 9ER trial explored the link between HRQoL and clinical outcomes at a median follow-up of 32.9 months (Abstract #384). These data provide further patient-focused context to the benefits of the combination of Cabometyx and nivolumab, whilst also reinforcing the association of the combination with an increased chance of tumor shrinkage, survival and progression-free survival, independent of early HRQoL deterioration.