IMDELLTRA® DEMONSTRATED SUPERIOR OVERALL SURVIVAL IN SMALL CELL LUNG CANCER

On April 11, 2025 Amgen (NASDAQ:AMGN) reported that the global Phase 3 DeLLphi-304 clinical trial evaluating IMDELLTRA (tarlatamab-dlle) as a treatment for patients with small cell lung cancer (SCLC) who progressed on or after a single line of platinum-based chemotherapy met its primary endpoint at a planned interim analysis (Press release, Amgen, APR 11, 2025, View Source [SID1234651892]). IMDELLTRA demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) compared to local standard-of-care (SOC) chemotherapy.

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"Small cell lung cancer is one of the most aggressive malignancies, with a high unmet need for more effective therapies.1 The topline results from DeLLphi-304 demonstrate overwhelming clinical benefit for people living with this devastating disease and affirm IMDELLTRA as standard of care," said Jay Bradner, M.D., executive vice president, Research and Development, at Amgen. "We look forward to sharing these results with the scientific community and health authorities as we continue our efforts to bring IMDELLTRA to patients worldwide."

The safety profile for IMDELLTRA was consistent with its known profile. Detailed data from DeLLphi-304 will be presented at an upcoming medical congress.

DeLLphi-304 is a global Phase 3 randomized controlled open-label clinical trial evaluating the efficacy and safety of IMDELLTRA as a treatment for patients with SCLC who progressed on or after a single line of platinum-based chemotherapy.2 Patients were randomized to receive either IMDELLTRA or local SOC chemotherapy (topotecan in all countries except Japan; lurbinectedin in the U.S., Canada, Australia, Singapore, Korea; and amrubicin in Japan).2,3 The primary outcome measure of the trial is OS.2

About IMDELLTRA (tarlatamab-dlle)
IMDELLTRA is a first-in-class immunotherapy engineered by Amgen researchers that binds to both DLL3 on tumor cells and CD3 on T cells, activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.4,5 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target.6,7

IMDELLTRA (tarlatamab-dlle) U.S. Indication
IMDELLTRA (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

About Small Cell Lung Cancer (SCLC)
SCLC is one of the most aggressive and devastating solid tumor malignancies, with a 5-10% five-year relative survival rate across all stages combined.1 SCLC comprises about 15% of the more than 2.4 million patients diagnosed with lung cancer worldwide each year.8-10 Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options.9

About Tarlatamab Clinical Trials
Amgen’s robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as both a monotherapy and in combination regimens in earlier lines of SCLC.

Tarlatamab is being investigated in multiple studies including DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard of care therapies in first-line ES-SCLC; DeLLphi-304, a randomized Phase 3 trial comparing tarlatamab monotherapy with standard of care chemotherapy in second-line treatment of SCLC; DeLLphi-305, a randomized Phase 3 trial comparing tarlatamab in combination with durvalumab versus durvalumab alone as first-line maintenance treatment in ES-SCLC; DeLLphi-306, a randomized placebo-controlled Phase 3 trial of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC; DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab in second line or later ES-SCLC; and DeLLphi-309, a Phase 2 study evaluating alternative intravenous dosing regimens with tarlatamab in second-line ES-SCLC.11

For more information, please visit www.tarlatamabclinicaltrials.com.

U.S. Food and Drug Administration Approves Opdivo® (nivolumab) plus Yervoy® (ipilimumab) as a First-Line Treatment for Unresectable or Metastatic Hepatocellular Carcinoma

On April 11, 2025 Bristol Myers Squibb (NYSE: BMY) reported that the U.S. Food and Drug Administration (FDA) approved Opdivo (nivolumab) plus Yervoy (ipilimumab) as a first-line treatment for adult patients with unresectable or metastatic hepatocellular carcinoma (HCC), the most common primary liver cancer (Press release, Bristol-Myers Squibb, APR 11, 2025, View Source;Food-and-Drug-Administration-Approves-Opdivo-nivolumab-plus-Yervoy-ipilimumab-as-a-First-Line-Treatment-for-Unresectable-or-Metastatic-Hepatocellular-Carcinoma/default.aspx [SID1234651893]). This approval is based on the results from the global Phase 3 randomized, open-label CheckMate-9DW trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of tyrosine kinase inhibitor monotherapy (lenvatinib or sorafenib) in patients with unresectable or metastatic HCC who have not received prior systemic therapy.1 In the trial, Opdivo plus Yervoy demonstrated statistically significant overall survival (OS) and overall response rate (ORR) vs the comparator arm.1 It is the only trial supporting an FDA approval to show superior results against this comparator arm.1

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"The CheckMate-9DW approval is an important advancement for patients, considering the incidence of liver cancer has tripled in the last four decades, yet prognosis for HCC patients remains poor," said Aiwu Ruth He, MD, PhD, a CheckMate-9DW study investigator while at MedStar Georgetown University Hospital.3,4 "The availability of a new first-line treatment option that demonstrated a deep response can offer adults with this form of liver cancer long-term overall survival and may help address an unmet need.1,5,6 Given the strength of evidence from the trial, especially considering the selection and performance of a strong comparator arm, I believe that Opdivo plus Yervoy has the potential to become a standard of care for the first-line treatment of patients with unresectable or metastatic HCC."1

In the CheckMate-9DW trial, in which 85% of patients in the comparator arm were treated with lenvatinib and 15% were treated with sorafenib, mOS with Opdivo plus Yervoy (n=335) was 23.7 months (95% CI: 18.8-29.4) vs. 20.6 months (95% CI: 17.5-22.5) with lenvatinib or sorafenib (n=333; HR=0.79; 95% CI: 0.65-0.96 P=0.0180), reducing the risk of death by 21%.1 Opdivo plus Yervoy showed an OS rate of 38% at three years vs. 24% with lenvatinib or sorafenib monotherapy.1 The trial also showed a deeper response with Opdivo plus Yervoy, demonstrating an ORR of 36.1% (95% CI: 31-41.5) compared to 13.2% (95% CI: 9.8-17.3; P<0.0001) of patients treated with lenvatinib or sorafenib (complete response 6.9% vs 1.8%; partial response 29.3% vs 11.4%).1 Longer responses were seen with Opdivo plus Yervoy with a median duration of response (mDOR) of 30.4 months (95% CI: 21.2-NR) and 12.9 months (95% CI: 10.2-31.2) with lenvatinib or sorafenib.1 DOR is not included in the statistical hierarchical testing and therefore is not a powered endpoint.1 The safety profile with Opdivo plus Yervoy is well-established and there were no new safety signals identified.5

Opdivo plus Yervoy is associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.1 Please see the Important Safety Information section below.

"Bringing Opdivo plus Yervoy to patients with HCC in the first-line setting is a testament to our ongoing commitment to research and delivering important progress for people living with cancer," said Wendy Short Bartie, senior vice president of Oncology Commercialization at Bristol Myers Squibb. "Today’s approval builds on the legacy of our dual immunotherapy and the value it has brought to patients for years.1 We are thrilled to add this indication for this important therapy – our second approval for Opdivo plus Yervoy in the gastrointestinal space this week alone – and look forward to providing a new first-line treatment option to patients in need."1

The combination of Opdivo plus Yervoy was previously granted accelerated approval by the U.S. FDA in 2020 based on results from the Phase 1/2 CheckMate-040 trial and has been an established second-line treatment for patients with advanced HCC who were previously treated with sorafenib.1 Today’s FDA decision converts this existing indication to full approval and expands the indication into the first-line setting based on the results from the CheckMate-9DW trial.1

About CheckMate-9DW
CheckMate-9DW is a Phase 3 randomized, open-label trial evaluating the combination of Opdivo (nivolumab) plus Yervoy (ipilimumab) compared to investigator’s choice of lenvatinib or sorafenib monotherapy in patients with unresectable or advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy.7 In the trial, 668 patients were randomized to receive Opdivo plus Yervoy IV infusion (Opdivo 1mg/kg with Yervoy 3mg/kg every three weeks for up to four doses, followed by Opdivo monotherapy 480mg every four weeks until disease progression, unacceptable toxicity or for a maximum duration of two years), or single agent lenvatinib (8mg orally daily, if body weight <60kg, or 12mg orally daily, if body weight ≥60kg) or sorafenib (400mg orally twice daily) in the control arm.1,5 The primary endpoint of the trial is overall survival and key secondary endpoints include objective response rate and time to symptom deterioration.1 The study was not designed to independently compare Opdivo plus Yervoy vs. lenvatinib or Opdivo plus Yervoy vs. sorafenib.1

Select Safety Profile from CheckMate-9DW
The safety analysis in CheckMate-9DW included 657 patients, of whom 332 received Opdivo plus Yervoy.1 Serious adverse reactions occurred in 53% of patients treated with Opdivo plus Yervoy.1 The most frequent non liver-related serious adverse reactions reported in ≥2% of patients who received Opdivo with Yervoy were diarrhea/colitis (4.5%), gastrointestinal hemorrhage (3%), and rash (2.4%). Liver-related serious adverse reactions occurred in 17% of patients treated with Opdivo in combination with Yervoy, including Grade 3-4 events in 16% of patients. The most frequently reported all grade liver-related serious adverse reactions occurring in ≥1% of patients who received Opdivo in combination with Yervoy were immune-mediated hepatitis (3%), increased AST/ALT (3%), hepatic failure (2.4%), ascites (2.4%), and hepatotoxicity (1.2%).1 The most common adverse reactions reported in >20% of patients treated with Opdivo plus Yervoy were rash, pruritus, fatigue, and diarrhea. Fatal adverse reactions occurred in 12 (3.6%) patients who received Opdivo plus Yervoy; these included 4 (1.2%) patients who died due to immune-mediated or autoimmune hepatitis and 4 (1.2%) patients who died of hepatic failure.1 Permanent discontinuation due to an adverse reaction occurred in 27% of patients treated with Opdivo in combination with Yervoy. Adverse reactions leading to permanent discontinuation in >1% of patients included immune-mediated hepatitis (1.8%), diarrhea/colitis (1.8%), and hepatic failure (1.2%).1

About Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is a type of primary liver cancer and is the most common form of liver cancer in adults.2 Liver cancer is the sixth leading cause of cancer deaths in the United States.8 HCC is often diagnosed at an advanced stage and is usually associated with poor prognosis with limited effective treatment options.5,9,10 About 42,240 people in the United Stated will be diagnosed and about 30,090 people will die of liver cancer in 2025.3 The incidence rates of liver cancer have tripled in the U.S. since 1980 and deaths have doubled since then.3 HCC typically develops in patients with hepatitis virus infection or cirrhosis.11 While most cases of HCC are caused by hepatitis B virus or hepatitis C virus infections, metabolic syndrome and metabolic dysfunction-associated steatohepatitis are rising in prevalence and expected to contribute to increased rates of HCC.11

INDICATIONS

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune- mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO or YERVOY and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. 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 OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO and YERVOY or YERVOY interruption or discontinuation is required, 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 corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%).

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%).

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%).

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. 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. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%).

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%).

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%).

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%).

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis.

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: nervous system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction; cardiovascular: angiopathy, temporal arteritis; ocular: blepharitis, episcleritis, orbital myositis, scleritis; gastrointestinal: pancreatitis (1.3%); other (hematologic/immune): conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.

Some ocular IMAR 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, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO or YERVOY and YERVOY prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO or YERVOY and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

There are no data on the presence of OPDIVO and YERVOY or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.

Serious Adverse Reactions

In CheckMate-9DW, serious adverse reactions occurred in 53% of patients receiving OPDIVO with YERVOY (n=332). The most frequent non liver-related serious adverse reactions reported in ≥2% of patients who received OPDIVO with YERVOY were diarrhea/colitis (4.5%), gastrointestinal hemorrhage (3%), and rash (2.4%). Liver-related serious adverse reactions occurred in 17% of patients receiving OPDIVO with YERVOY, including Grade 3-4 events in 16% or patients. The most frequently reported all grade liver-related serious adverse reactions occurring in ≥1% of patients who received OPDIVO with YERVOY were immune-mediated hepatitis (3%), increased AST/ALT (3%), hepatic failure (2.4%), ascites (2.4%), and hepatoxicity (1.2%). Fatal adverse reactions occurred in 12 (3.6%) patients who received OPDIVO with YERVOY; these included 4 (1.2%) patients who died due to immune-mediated or autoimmune hepatitis and 4 (1.2%) patients who died of hepatic failure. In CheckMate-40, serious adverse reactions occurred in 59% of patients receiving OPDIVO with YERVOY (n=49). Serious adverse reactions reported in ≥4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis.

Common Adverse Reactions

In CheckMate-9DW, the most common adverse reactions (>20%) in patients receiving OPDIVO with YERVOY (n=332) were rash (36%), pruritus (34%), fatigue (33%), and diarrhea (25%). In CheckMate-040, the most common adverse reactions (≥20%) in patients receiving OPDIVO with YERVOY (n=49) were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and weight decreased (20%).

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY.

Clinical Trials and Patient Populations

CheckMate-9DW – hepatocellular carcinoma, in combination with YERVOY; CheckMate-040 – hepatocellular carcinoma, in combination with YERVOY, after prior treatment with sorafenib.

Exicure, Inc. (Nasdaq: XCUR) Announces Their Next Step in Planning for a New Clinical Trial in Acute Myeloid Leukemia (AML)

On April 11, 2025 Exicure, Inc. (Nasdaq: XCUR) reported updates on its lead asset, GPC-100 (burixafor), a small molecule CXCR4 inhibitor (Press release, Exicure, APR 11, 2025, View Source [SID1234651894]).

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Exicure, Inc. ("Exicure") is planning for a clinical trial in Acute Myeloid Leukemia (AML) with GPC-100. The company believes that GPC-100, when paired with modern AML treatment regimens, can further improve outcomes in this high unmet need clinical indication. A Phase 1 chemosensitization study involving 15 patients with relapsed or refractory AML was previously conducted by Taigen, the original developer of GPC-100. In that study, GPC-100 was combined with fludarabine and cytarabine to evaluate safety and preliminary efficacy. Preclinical data published by Dr. Pam Becker at City of Hope in collaboration with GPCR Therapeutics USA, a subsidiary of Exicure, demonstrated that dual inhibition of CXCR4 with GPC-100 and beta-2 adrenergic receptor blockade led to improved chemotherapy response (2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual meeting : Poster #2758). This therapeutic approach is protected by an expanded patent portfolio granted in the United States, Japan, Australia, and Taiwan.

In addition to AML, GPC-100 is currently being evaluated in an ongoing Phase 2 trial in patients with multiple myeloma (MM) undergoing autologous stem cell transplant (ASCT; NCT05561751). Clinical trial results for this study are expected in Q4 2025.

Current Evaluating Potential Indication Expansions – In addition to AML and MM, Exicure is evaluating a range of potential indications for GPC-100, including sickle cell disease, pediatric oncology, and cell and gene therapy settings.

RedHill Biopharma Announces Full-Year 2024 Financial Results and Operational Highlights

On April 10, 2025 RedHill Biopharma Ltd. (NASDAQ: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported its full-year 2024 financial results and operational highlights and associated filing of its annual report on Form 20-F for the year ended December 31, 2024 (Press release, RedHill Biopharma, APR 10, 2025, View Source [SID1234651876]).

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Dror Ben-Asher, RedHill’s Chief Executive Officer, said: "We have undergone an extensive overhaul reshaping ourselves financially, operationally and strategically. Major corporate and R&D moves, undertaken over the last 12 months, have resulted in new and clearer opportunities to deliver maximum value from both our commercial and R&D assets. The potential $60 million ex-North America global license of RHB-102 to Hyloris lays the groundwork for the ongoing development and commercialization in the large gastroenteritis, oncology support and IBS-D markets while enabling RedHill to maintain control of the key North American markets. The approximately $8 million plus legal costs New York Supreme Court summary judgment was a resounding win for RedHill and we are fully committed to pursuing the collection of this award. Last year’s recommendation by the latest ACG Clinical Guideline for Talicia as a first-line therapeutic option for H. pylori eradication, has, we expect further enhanced Talicia’s product profile as the leading branded U.S. gastroenterologist prescribed H. pylori therapy, winning additional formulary successes securing 25 million covered lives. After its successful launch in UAE, Talicia is also poised for a potential UK Marketing Authorisation Application (MAA) mid-year, presenting a promising pathway for Talicia’s entry into additional markets globally."

Mr. Ben-Asher continued: "Having successfully completed the Hyloris RHB-102 out-license deal, we are now advancing our next-generation candidate, RHB-204, in the $12 billion Crohn’s disease space, employing a novel, groundbreaking approach, supported by RHB-104’s positive Phase 3 clinical data. In parallel, opaganib continues to show its broad-acting potential and we are very excited to have initiated the innovative Bayer-supported Phase 2 study in combination with darolutamide, which may bring vital new hope to men with metastatic castrate resistant prostate cancer. Progress was also made with opaganib as a treatment for GI-ARS following positive results from new in vivo studies, undertaken as part of the U.S. government’s Radiation and Nuclear Countermeasures Program (RNCP) product pipeline development contract, further confirming opaganib’s radioprotective activity in models of GI-ARS. Discussions are ongoing regarding advanced development. Additionally, the ongoing U.S. Government-supported work in Ebola continues following our previously announced BARDA grant. We have started 2025 as we mean to go on – aggressively pursuing our business goals and aiming to deliver on our catalysts in a meaningful way."

Financial results for the 12 months ended December 31, 20242

Net Revenues for the year ended December 31, 2024 were $8.0 million, compared to $6.5 million for the year ended December 31, 2023. Talicia net revenues for the year ended December 31, 2024, increased to $9.0 million from $8.8 million for the year ended December 31, 2023, driven by approximately $1.0 million of revenues generated from the UAE partnership with Gaelan Medical. Net revenues for the years ended December 31, 2024 and December 31, 2023 included Movantik contra-revenues of $0.9 million and $2.6 million for Movantik, respectively, mainly due to product returns.

Cost of Revenues for the year ended December 31, 2024 was $3.2 million, compared to $3.5 million for the year ended December 31, 2023. The decrease was primarily due to lower inventory write-downs, which totaled $0.2 million in 2024 compared to $1.3 million in 2023.

Gross Profit for the year ended December 31, 2024 was $4.9 million, compared to $3.1 million for the year ended December 31, 2023, reflecting the increase in net revenues and the lower level of inventory write-downs in 2024.

Research and Development Expenses for the year ended December 31, 2024 were $1.6 million, as compared to $3.5 million for the year ended December 31, 2023. The decrease was attributable to the costs from closing the RHB-204 clinical trial, which were recognized in 2023, as well as ongoing cost-reduction measures.

Selling, Marketing, and General and Administrative Expenses for the year ended December 31, 2024 were $15.5 million, as compared to $31.0 million for the year ended December 31, 2023. The reduction was primarily attributable to ongoing cost-reduction measures and the divestment of Movantik in 2023, which led to workforce downsizing and other related expense reductions.

Other Expenses for the year ended December 31, 2024 were $2.3 million, recognized as part of the Global Termination Agreement3, as compared to Other Income of $44.1 million for the year ended December 31, 2023. The Other Income in 2023 was comprised of (i) $35.5 million from the divestiture of Movantik, calculated as the difference between the fair value of the rights and the carrying amount of this asset and (ii) $8.6 million from transitional services provided to the buyer of Movantik.

Operating Loss for the year ended December 31, 2024 was $14.6 million, compared to Operating Income of $12.6 million for the year ended December 31, 2023. Both periods include items related to the Movantik divestiture, as described under Other Expenses – a $2.3 million loss in 2024 and $44.1 million income in 2023. Excluding these, the year-over-year change reflects improved operating performance driven by cost-cutting measures.

Financial Income, net for the year ended December 31, 2024 was $6.3 million, compared to Financial Income, net of $11.3 million for the year ended December 31, 2023. The income recognized for the year ended December 31, 2024, was primarily driven by the revaluation of financial instruments, partially offset by other financing expenses. The income recognized in the year ended December 31, 2023, was primarily attributable to a $20.6 million gain resulting from the extinguishment of the HCRM debt in exchange for the transfer of rights to Movantik, calculated as the difference between the carrying amount of the financial liability and the fair value of the rights transferred, partially offset by financial expenses related to the financial instruments and other financial expenses.

Net Loss for the year ended December 31, 2024 was $8.3 million, as compared to Net Income of $23.9 million for the year ended December 31, 2023. Both periods include impacts from the Movantik divestiture, as detailed under Other Expenses and Financial Income – a $2.3 million loss in 2024 and $64.7 million in income in 2023. Excluding these, the year-over-year change reflects improved performance driven by cost cutting measures.

Total Assets as of December 31, 2024 were $18.0 million, as compared to $23.0 million as of December 31, 2023. The decrease was primarily attributable to the decrease in cash balance, reduced inventory and a decline in prepaid expenses and other receivables, consistent with the Company’s scaled-down operations, as well as impact of balances settled as part of the Global Terminations Agreement, and a reduction in right-of-use assets following the termination of vehicle leases during 2024.

Total Liabilities as of December 31, 2024 were $22.7 million, as compared to $21.0 million as of December 31, 2023. The increase primarily reflects the impact of the Global Termination Agreement, under which the Company incurred liabilities related to Movantik that were allocatable to HCRM and its affiliates under their agreements with the Company, offset by payments made toward these liabilities during the period. Additionally, there was an increase in derivative financial instruments associated with warrant liabilities from offerings made during 2024. This was partially offset by a decrease in accounts payable and allowance from deductions from revenues, consistent with the Company’s scaled-down operations, as well as a reduction in lease liabilities due to the termination of car leases.

Net Cash Used in Operating Activities for the year ended December 31, 2024 was $9.4 million, compared to $35.8 million for the year ended December 31, 2023. The cash used in operating activities was primarily directed towards settling pre-closing liabilities related to Movantik and other operational activities. This was partially offset by proceeds received from the Global Termination Agreement, net of payments made to settle obligations arising from this agreement.

Net Cash Provided by Financing Activities for the year ended December 31, 2024 was $8.4 million, primarily generated through equity offerings. Net Cash Provided by Financing Activities for the year ended December 31, 2023, was $21.4 million, comprised primarily of proceeds from equity offerings and exercise of certain warrants in transactions consummated in each of April 2023, July 2023, September 2023 and November 2023, and from decrease in restricted cash, partially offset by repayment of payables in respect of intangible asset purchases.

Cash Balance as of December 31, 2024, was $4.8 million1.

Commercial and R&D Highlights:

Commercial – streamlined and revenue-generating:

With a significantly streamlined commercial operation, Talicia has generated net revenues of $9.0 million, supported by approximately $1.0 million of new revenues from the UAE partnership with Gaelan Medical, and remains the leading U.S. gastroenterologist-prescribed branded H. pylori therapy.

Significant effort has resulted in important accomplishments with Talicia, such as the inclusion as first-line option for treatment of H. pylori infection in the recently updated 2024 American College of Gastroenterology (ACG) Clinical Guideline, the securing of 25 million covered lives following the Medi-Cal renewal and Humana formulary win, a successful launch in the UAE and the potential for opening up new markets with the recently announced plan for a Talicia UK MAA. Talicia has now surpassed the 100,000 prescriptions milestone and our innovative warranty program, with minimal refunds claimed, reflects a positive patient experience.

R&D – focused on new opportunities:

Largely externally funded, with multiple U.S. Government and non-governmental collaborations, RedHill’s pipeline provides new and exciting opportunities in major indications: Crohn’s disease, prostate cancer, diabetes and obesity-related disorders, Ebola and other viral and pandemic preparedness indications as well as for gastrointestinal-acute radiation syndrome (GI-ARS) and other medical/chemical countermeasure uses:

Opaganib4:

A potentially broad acting, novel, oral, host-directed small molecule drug, with a demonstrated safety and efficacy profile, advancing in predominantly U.S. Government-supported, externally funded programs, directed at multiple underserved indications with sizeable multi-billion-dollar market opportunities and potentially advantageous pathways to approval.

Opaganib is in development for multiple oncology, viral, inflammatory and diabetes and obesity-related indications, including prostate cancer, COVID-19, Ebola, acute respiratory distress syndrome (ARDS) and radio/chemical protection, including GI-ARS:

A new approach in the $12 billion prostate cancer market:

Prostate cancer (PC) is the second most diagnosed cancer in the world, with around 1.5 million new cases per year, causing almost 400,000 deaths5. People with metastatic castrate-resistant prostate cancer (mCRPC) have few treatment options available to them.

In February 2025, the Company announced the initiation of a Bayer-supported Phase 2 study of opaganib in combination with Bayer’s darolutamide in mCRPC, evaluating the potentially enhancing effect of opaganib in patients with poor prognosis.

The study will utilize a companion lipid biomarker test (PCPro) to select mCRPC patients who have a poor prognosis due to standard of care (SoC) treatment and who may benefit from an opaganib + darolutamide combination treatment approach. The primary endpoint will be improved 12-month radiographic progression-free survival (rPFS).

Other opaganib programs/updates include:

U.S. Army and BARDA-grant funded program for Ebola. Opaganib is believed to be the first host-directed molecule to show activity in vivo in Ebola virus disease, delivering a statistically significant increase in survival and, separately, demonstrating a robust synergistic effect in vitro when combined with remdesivir (Veklury; Gilead Sciences, Inc.), improving viral inhibition while maintaining cell viability
U.S. Government- and non-government funded programs ongoing with the NIH / BARDA-funded nuclear and chemical medical countermeasure programs for GI-ARS and Phosgene inhalation injury. On December 10, 2024, the Company announced positive results from new in vivo studies of opaganib as a treatment for GI-ARS, undertaken as part of the U.S. Government’s Radiation and Nuclear Countermeasures Program (RNCP) product pipeline development contract. These results further confirm opaganib’s protective activity in models of GI-ARS and discussions are ongoing regarding advanced development.
Positive in vivo study results support potential of opaganib therapy in diabetes / obesity-related disorders – a market projected to be worth approximately $100 billion within the next decade. ‘Opaganib Promotes Weight Loss and Suppresses High-Fat Diet-Induced Obesity and Glucose Intolerance’ was recently published6 in the journal Diabetes, Metabolic Syndrome and Obesity
Orphan drug designation granted by FDA for neuroblastoma (opaganib has several such designations in multiple indications, with three in oncology)
ARDS, COVID-19 and Influenza programs continue to seek to address multi-hundreds of millions of dollars markets
RHB-204:

RHB-204 is a proprietary, fixed-dose oral capsule containing a combination of clarithromycin, rifabutin and clofazimine, at specific doses designed to safely and effectively treat Mycobacterium avium subspecies paratuberculosis-positive (MAP-positive)-related Crohn’s disease (CD). Unlike existing therapies that focus on symptom relief, RHB-204 is intended to target the possible root cause of Crohn’s disease, which is hypothesized to be caused by Mycobacterium avium subspecies paratuberculosis (MAP).

Patent protected until at least 2041, RHB-204 is a next-generation formulation of RHB-104, which successfully completed a Phase 3 study in Crohn’s disease, with an optimized formulation for the treatment of CD. It contains the same three antimicrobial agents with potent intracellular, anti-mycobacterial and anti-inflammatory properties, and with an optimized dosing profile, RHB-204 provides the potential for enhanced tolerability, safety and compliance with a 40% pill burden reduction. RHB-204 is supported by a strong foundation of clinical data from the positive safety and efficacy results achieved in the Phase 3 study of RHB-104 in CD, with its potential further demonstrated using mucosal healing imaging, considered to be the gold standard for efficacy evaluation in CD.

Paradigm shift in MAP-positive CD treatment approach

In March 2025, the Company announced its plans to advance its potentially groundbreaking late-stage RHB-204 Crohn’s disease program, building on statistically significant positive RHB-104 Phase 3 results. FDA guidance on pathway to approval is anticipated in the coming weeks. RedHill is actively pursuing funding opportunities and partnerships to advance this potential paradigm-shifting treatment.

The planned innovative Phase 2 study of RHB-204 is planned to be the first ever clinical study in CD patients who are all MAP-positive and will evaluate mucosal healing, a new gold standard in assessing efficacy in Crohn’s disease, and MAP eradication utilizing novel and decisive endpoints and imaging, allowing for a study design with a relatively small sample size.

RHB-204 builds upon RHB-104’s successful Phase 3 study, which successfully met its Phase 3 study primary and secondary endpoints demonstrating a statistically significant 64% improvement in efficacy versus standard of care. It also showed compelling mucosal healing data in CD patients who underwent colonoscopy. The inclusion of MAP-positive only patients in the planned study with RHB-204 is anticipated to demonstrate a more consistent benefit in the study population across all efficacy outcomes.

RHB-107 (upamostat) update:

On January 30, 2025, we were notified that funding from the U.S. Government Department of Defense’s Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) for the ongoing 300-patient Phase 2 RHB-107 arm of the ACESO PROTECT platform trial for early COVID-19 outpatient treatment was subject to termination, requiring the study to cease enrollment on Feb 28, 2025. 93 patients have been enrolled out of a fully enrolled target patient population of 300. Due to the reduced number of patients enrolled in this study, the study result may not lead to conclusions regarding the efficacy of RHB-107 in this trial.

The U.S. Army-funded Ebola development program remains ongoing, with RHB-107 having demonstrated a robust synergistic effect in vitro when combined with remdesivir. Management of potential Ebola virus pandemic outbreaks represents a significant opportunity and is a key concern for global health agencies.

Annual Report:

A copy of the Company’s annual report on Form 20-F for the year ended December 31, 2024 has been filed with the U.S. Securities and Exchange Commission at View Source and posted on the Company’s investor relations website at:
View Source

IDEAYA Biosciences Announces Phase 1/2 Expansion for IDE397 and Trodelvy® Combination in MTAP-Deletion Urothelial Cancer

On April 10, 2025 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported the initiation of a Phase 1/2 expansion in the clinical trial evaluating IDE397, its investigational, potential first-in-class, small molecule methionine adenosyltransferase 2a (MAT2A) inhibitor, in combination with Gilead’s Trodelvy (sacituzumab govitecan-hziy), a Trop-2 directed antibody-drug conjugate (ADC), in methylthioadenosine phosphorylase (MTAP)-deletion urothelial cancer (UC) based on preliminary safety and clinical efficacy data (Press release, Ideaya Biosciences, APR 10, 2025, View Source [SID1234651877]).

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IDE397 is a potent and selective small molecule inhibitor targeting (MAT2A), in patients having solid tumors with MTAP-deletion. The prevalence of MTAP-deletion is estimated to be approximately 26% in UC.

"We are pleased to advance the potential first-in-class clinical combination of IDE397 and Trodelvy into an initial Phase 1/2 expansion in MTAP-deletion UC based on preliminary safety and clinical efficacy observed. We are excited to continue to explore this novel combination given the high unmet medical need, as there are no approved therapies specifically for MTAP-deletion UC," said Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer. The use of Trodelvy in MTAP-deletion UC is investigational, and the safety and efficacy of this use have not been established.

A clinical program update on the IDE397 and Trodelvy combination is planned in 2025. In addition to the clinical trial program evaluating IDE397 in combination with Trodelvy, IDEAYA is has a monotherapy expansion study in MTAP-deletion NSCLC and UC and is expecting to initiate a wholly-owned clinical combination trial of IDE397 and IDE892, IDEAYA’s potential best-in-class, MTA-cooperative PRMT5 inhibitor in the second half of 2025.

Pursuant to the clinical study collaboration and supply agreement, IDEAYA and Gilead retain the commercial rights to their respective compounds, including with respect to use as a monotherapy or combination agent. IDEAYA is the study sponsor and Gilead will provide the supply of Trodelvy to IDEAYA.

IDE397 monotherapy or in combination with Trodelvy has not been approved by any regulatory agency and the efficacy and safety of this combination has not been established.

Trodelvy and Gilead are trademarks of Gilead Sciences, Inc., or its related companies.