On December 9, 2023 Orca Bio, a late-stage biotechnology company developing high-precision cell therapies for the treatment of cancer, autoimmune diseases and genetic blood disorders, reported positive new data that suggest its investigational high-precision cell therapies, Orca-T and Orca-Q, have the potential to deliver improved clinical outcomes across different age ranges, donor types and conditioning regimens relative to existing standard of care allogeneic hematopoietic stem cell transplants (alloHSCT) (Press release, Orca Bio, DEC 9, 2023, View Source;utm_medium=rss&utm_campaign=orca-bio-presents-positive-data-demonstrating-the-potential-for-orca-t-and-orca-q-to-expand-treatment-to-additional-patient-groups-at-the-65th-ash-annual-meeting [SID1234638331]). The results presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting showed promising data with the use of Orca Bio’s cell therapies across several patient groups where there is significant unmet medical need.

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Orca-T in Older Patients with Myeloablative Conditioning

Results highlighted in an oral presentation showed Orca-T’s ability to deliver similar outcomes in older patients undergoing myeloablative conditioning (MAC) as younger patients. Notably, Orca-T delivered similar results across disease control, non-relapse mortality (NRM) and overall survival (OS).

"While the use of MAC offers the best chance of a cure, it also increases life-threatening complications in older patients receiving standard of care alloHSCT," said presenting author Caspian Oliai, M.D., medical director of the UCLA Bone Marrow Transplantation Stem Cell Processing Center. "These latest findings suggest a cell therapy like Orca-T, which has the potential to offer a cure while reducing toxicity and lowering treatment-related mortality, may allow older patients to better tolerate MAC. This approach could expand curative treatment to older patients who might not be offered a MAC regimen today, and potentially provide physicians with an important new option in our ongoing efforts to balance the risk of relapse with transplant-related side effects."

In a subgroup analysis, 64 patients from Orca Bio’s ongoing multi-center Phase 1b clinical trial who received Orca-T and busulfan, fludarabine and thiotepa (BFT) conditioning for the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype leukemia, chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) were divided into two age groups: 18-54 years of age (n=39), and 55 years of age and older (n=25). With a median follow-up of 12 months, the following outcomes were reported:

Relapse-free survival (RFS) was 84.8% in younger patients and 82.3% in older patients.
NRM was 0% in both groups.
OS was 100% and 95.5% in the younger and older patient groups, respectively.
Events of grade 3-4 acute graft versus host disease (GvHD) and moderate-to-severe chronic GvHD were low across the younger group (0 and 3, respectively) and older group (1 and 3, respectively).
Across all patients, Orca-T continued to be manufactured reliably and delivered with vein-to-vein times of 72 hours or less across the U.S.

Orca-T in Older Patients with Reduced Intensity Conditioning

Additional data from a single-center open-label Phase 1 clinical trial presented at ASH (Free ASH Whitepaper) looked at the outcomes of older patients treated with Orca-T and a reduced intensity conditioning (RIC). These patients were found to be unfit for a MAC regimen due to the significant risks associated with it, particularly in older age. At 12 months, patients treated with a RIC Orca-T (n=15) saw no observable compromise in curative outcomes, with no patients experiencing relapse (0%). Patients also saw encouraging RFS (79%) and a low incidence of both grade 3-4 acute and chronic GvHD (0% and 7%, respectively).

Collectively, these findings support the potential for Orca-T to treat older patients with hematological malignancies, whether they are given a MAC or RIC regimen, with no new safety signals reported.

Orca-T in Patients with MDS

New data was also presented on the performance of Orca-T in patients with intermediate to high-risk MDS. Current treatments for MDS aren’t often curative, and many patients relapse or become resistant to first-line treatment. There remains an unmet need for new, more effective but tolerable strategies to manage MDS.

In this subgroup from the ongoing multi-center Phase 1b clinical trial, Orca-T demonstrated promising results in this patient population (n=16). At one year, RFS with Orca-T was 94%. No patients experienced grade 3-4 acute GvHD, and moderate-to-severe chronic GvHD occurred in two patients. The rates of NRM and OS with Orca-T were 0% and 94%, respectively.

Orca-T is currently being evaluated in a pivotal Phase 3 clinical study for the treatment of AML, ALL and MDS at leading transplant centers across the U.S.

Orca-Q for Patients with Haploidentical Donors

In an oral presentation, Orca Bio shared updated data from a multi-center Phase 1 clinical trial of its second high-precision cell therapy, Orca-Q, in patients with a haploidentical donor without the use of post-transplant cyclophosphamide (PTCy).

"Orca-Q is a first-in-class therapy that has the potential to improve patient outcomes and reduce the risk of graft versus host disease without the use of PTCy," said presenting author Samer Srour, M.D., M.S., Department of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center. "While PTCy has increased the use of haploidentical HSCTs, it can bring a myriad of risks and toxicities that we didn’t experience with Orca-Q. These updated results in an expanded group of patients continue to support Orca-Q’s promise to overcome the challenges of haploidentical stem cell transplant by providing a solution where patients and physicians may no longer have to compromise between the risk of relapse and the risk of GvHD."

The positive outcomes from an expanded group of 33 patients with AML, ALL and CML support Orca-Q as a potential treatment option for patients with a haploidentical donor. With a median of 375 days follow-up, updated safety and efficacy data include:

No patients experienced moderate-to-severe chronic GvHD (0%).
There was one event of grade 3 acute GvHD and no grade 4 acute GvHD.
NRM was 9%.
RFS, GRFS and OS at one year were 82%.
Additionally, no new safety signals were identified. The estimated incidence of CTCAE grade 2 and greater than grade 3 infections at one year were 9% and 15%, respectively.

"At Orca Bio, we understand the challenges providers face in achieving the right balance in offering blood cancer patients the best option for a cure with optimal quality of life," said Ivan Dimov, Ph.D., co-founder and chief executive officer of Orca Bio. "We are pleased to present these latest findings at ASH (Free ASH Whitepaper) that add to our growing body of clinical evidence which underscore the potential of our novel high-precision platform to expand potentially life-saving treatment to more patient groups who could benefit."

The full ASH (Free ASH Whitepaper) presentations will be made available on www.orcabio.com.

About Orca-T
Orca-T is an investigational high-precision allogeneic cell therapy being evaluated in clinical trials for the treatment of multiple hematologic malignancies. Orca-T includes infusions containing regulatory T-cells, CD34+ stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors. Orca-T is currently being evaluated in a pivotal Phase 3 clinical trial at leading transplant centers across the U.S. and has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration.

About Orca-Q
Orca-Q is an investigational high-precision allogeneic cell therapy being evaluated in clinical trials for the treatment of hematologic malignancies in patients with haploidentical donors. Orca-Q is a proprietary composition of stem cells combined with specific T-cell subsets derived from healthy donors and engineered by Orca Bio’s high-precision platform. Orca-Q has the potential to improve patient outcomes and reduce the risks of toxicities without the use of post-transplant cyclophosphamide (PTCy) in patients unable to identify a full human leukocyte antigen (HLA) match.

On December 9, 2023 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported a poster presentation at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition featuring follow-up data from its Phase 1 clinical trial that evaluates NKX101 in patients with relapsed or refractory acute myeloid leukemia (r/r AML) (Press release, Nkarta, DEC 9, 2023, View Source [SID1234638329]). NKX101 is an allogeneic, off-the-shelf NK cell therapy candidate derived from healthy donors and engineered to target NKG2D ligands.

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As reported in June 2023, of those patients who received NKX101 after a disease-specific lymphodepletion (LD) regimen comprising fludarabine and cytarabine (Flu/Ara-C), four of six achieved CR/CRi. In the follow up presented today, three of those four patients remained in CR/CRi at 4 months from treatment with NKX101. No cases of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD) of any grade were observed in these patients.

"While this data set is small, we’re encouraged to see responses and early durability in patients with high-risk features, including those who have relapsed after stem cell transplantation. Recent progress in therapy for r/r AML has been limited to targeted therapies, which only help a minority of patients. This all-comers study seeks to help patients without targetable mutations as well as those for whom these treatments are ineffective," noted David R. Shook, MD, Chief Medical Officer of Nkarta. "We continue to evaluate NKX101 following Flu/Ara-C in this high-need patient population."

Nkarta plans to provide an update from the NKX101 Flu/Ara-C LD cohort in the first half of 2024 that includes preliminary safety and response data from 12 to 20 additional patients.

Nkarta’s 2023 ASH (Free ASH Whitepaper) poster will be available for download shortly after its scheduled presentation at View Source

About NKX101
NKX101 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy donors. It is engineered with a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. NKX101 is also engineered with a membrane-bound form of interleukin-15 (IL15) for greater persistence and activity without exogenous cytokine support.

On December 9, 2023 Genmab A/S (Nasdaq: GMAB) and AbbVie (NYSE: ABBV) reported new data from the ongoing phase 1/2 EPCORE NHL-1 clinical trial investigating epcoritamab (DuoBody CD3xCD20), a T-cell engaging bispecific antibody administered subcutaneously, demonstrated an overall response rate (ORR) of 82 percent, a complete response (CR) rate of 63 percent and minimal residual disease (MRD) negativity rate of 67 percent in patients with relapsed/refractory (R/R) follicular lymphoma (FL) (Press release, Genmab, DEC 9, 2023, View Source [SID1234638325]). The presentation included data from an optimized step-up dosing schedule for FL patients showing a reduction in risk and severity of Grade 2+ cytokine release syndrome (CRS), a common side effect of T-cell engaging cancer treatments. These results were presented today at the 2023 65th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), being held in San Diego, California, December 9-12, 2023 (Abstract #1655).

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"Despite treatment advances for patients with follicular lymphoma whose disease has unfortunately progressed, treating relapsed or refractory follicular lymphoma remains highly challenging, particularly in the third-line plus setting," said Catherine Thieblemont, M.D., Ph.D., head of the hemato-oncology department, Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris (APHP) in Paris. "The patients in this trial represent a historically difficult-to-treat patient population. The data presented today are especially notable because they demonstrated high overall and complete response rates for this investigational follicular lymphoma therapy and a preview for its potential as an alternative treatment option."

Overall results from the pivotal cohort of 128 adult patients showed that:

At a median follow-up of 17.4 months, the study’s primary endpoint ORR was 82 percent, which exceeded the protocol defined threshold for efficacy, with a CR rate of 63 percent, and 67 percent MRD negativity.
The median time to response was 1.4 months and median time to CR was 1.5 months.
Median progression-free survival (PFS) for patients who achieved a CR was not reached nor was the median duration of response, duration of CR, MRD negativity and overall survival.
An estimated 85 percent and 74 percent of patients who experienced a CR remained in response at 12 and 18 months, respectively.
Among prespecified subgroups, ORR and CR rates were generally consistent with the overall patient population. Notably, high-risk patients who were refractory to both anti-CD20 therapy and an alkylating agent achieved a 76 percent ORR and 56 percent CR; patients who were refractory to last prior treatment achieved a 74 percent ORR and 51 percent CR rate; and patients whose disease progressed within two years of first-line immunochemotherapy (POD24) achieved an 80 percent ORR and 61 percent CR.

Safety findings were consistent with previous epcoritamab trials, and epcoritamab was generally well tolerated. Following an optimized step-up dose regimen for FL patients (n=50) to reduce the risk and severity of CRS, 40 percent of patients experienced Grade 1 CRS and 8 percent experienced Grade 2 (no Grade 3 or higher CRS were reported) and no Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was reported. This data may support outpatient administration. Additional common treatment-emergent adverse events (TEAEs) from the pivotal cohort (>20 percent) were injection-site reaction (57 percent), COVID-19 (40 percent), fatigue (30 percent), neutropenia (29 percent), diarrhea (27 percent) and pyrexia (25 percent). TEAEs leading to treatment discontinuation occurred in 19 percent of patients, and Grade 5 TEAEs occurred in 13 patients (10 percent).

"Follicular lymphoma patients who have experienced a relapse following heavy pre-treatment, or whose disease is not responding to available therapies, are considered high risk and are in need of alternative therapeutic options," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "The data presented at ASH (Free ASH Whitepaper) reinforce what we have seen from our epcoritamab research and believe that this investigational bispecific antibody could potentially represent an important treatment option for patients living with relapsed or refractory follicular lymphoma. Along with our partner AbbVie, we look forward to progressing epcoritamab in clinical trials and discussing the results with regulatory authorities and remain committed to developing epcoritamab as a potential future core therapy for B-cell malignancies."

About the Phase 1/2 EPCORE NHL-1 Trial
EPCORE NHL-1 an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a phase 1 first-in-human, dose escalation part; a phase 2a expansion part; and a phase 2a dose optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin’s lymphoma (B-NHL), including FL. In the phase 2a expansion part, additional patients were enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who have limited therapeutic options. The dose optimization part evaluates the potential for alternative step-up dosing regimens to help further minimize Grade 2 cytokine release syndrome (CRS) and mitigate Grade ≥3 CRS. The primary endpoint of the expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included DOR, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints.

About Follicular Lymphoma (FL)
FL is typically an indolent (or slow growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.i FL is the second most common form of NHL overall, accounting for 20-30 percent of all NHL cases, and represents 10-20 percent of all lymphomas in the western world.i,ii,iii Although FL is an indolent lymphoma, it is considered incurable with conventional therapyiv,v and patients who achieve remission also often experience relapse.vi

About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.vii

Epcoritamab (approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU) has received regulatory approval in certain lymphoma indications in several territories. Use of epcoritamab in FL is not approved in any country, including the U.S. and the EU. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes three ongoing phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494) compared to investigators choice chemotherapy, a phase 3 trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL (NCT: 05578976), and a phase 3, open-label clinical trial evaluating epcoritamab in combination with rituximab and lenalidomide in patients with R/R FL (NCT: 05409066). Epcoritamab is not approved to treat newly diagnosed patients with DLBCL or FL. The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit clinicaltrials.gov for more information.

On December 9, 2023 FibroGen, Inc. (NASDAQ: FGEN) reported the presentation of efficacy and safety data from MATTERHORN, a Phase 3 clinical study of roxadustat for the treatment of anemia in patients with lower risk transfusion-dependent myelodysplastic syndromes (MDS) at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held in San Diego, California December 9 – 12, 2023 (Press release, FibroGen, DEC 9, 2023, View Source [SID1234638324]). The oral presentation was selected for the "2024 Highlights of ASH (Free ASH Whitepaper)".

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"We are excited to have our data selected for presentation as part of the 2024 Highlights of ASH (Free ASH Whitepaper). We believe that roxadustat could represent an important new therapy for patients with higher transfusion burden low-risk-MDS," said Thane Wettig, Chief Executive Officer, FibroGen. "There continues to be a significant unmet need in this patient population, and the novel mechanism of roxadustat delivered orally three times a week could represent an important new and convenient treatment alternative."

As previously disclosed, the initial analysis with all the patients who participated in the trial, showed that more patients receiving roxadustat achieved transfusion independence vs. placebo (48% vs. 33%; p=0.22). While the primary endpoint of transfusion independence (TI) for ≥ 56 consecutive days within the first 28 weeks of the study was not met, a post-hoc analysis, showed that roxadustat performed significantly betterǂ than placebo in the subset of patients having higher transfusion burdenǂǂ (see table). The TI for ≥56 days within the first 28 weeks of the study was 36.1% for the roxadustat group and 11.5% for the placebo group (p=0.047ǂ), and 44.4% vs 19.2% at the end of trial, respectively. Additionally, in TI responders, more patients in the roxadustat arm vs. placebo had hemoglobin concentration increases of ≥1.5 g/dL: 45.5% vs 17.4% (p=0.004)ǂ.

% (95% CI) Roxadustat (n=36) Placebo (n=26) Roxadustat vs Placebo
TI for ≥56 days within 28 weeks 36.1%
(20.8–53.8) 11.5%
(2.4-30.2) OR: 3.823 (0.96–15.20),
p=0.047ǂ
TI for ≥56 days by EOT 44.4% (27.9–61.9) 19.2%
(6.6–39.4) OR: 3.369 (1.01–11.19)
p=0.048ǂ
ǂNominal statistical significance

ǂǂHigher transfusion burden defined as ≥2 pRBC units Q4W

"The results seen from roxadustat in the subset of patients having higher transfusion burden are intriguing," said Moshe Mittelman M.D., Professor of Medicine and Hematology at Tel Aviv Sourasky Medical Center and MATTERHORN principal investigator. "Based on these results, roxadustat may be an option in anemia of low risk-MDS which can further be explored in a confirmatory study focused on higher burden transfusion-dependent patients. There is a significant opportunity in this patient population for an effective oral treatment such as roxadustat, and if approved it would be an important advancement for the field."

Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, was generally well tolerated, with treatment emergent adverse events of any grade similar across treatment groups. Overall, the adverse event profile that was observed during the double-blind portion of the study was generally consistent with previous findings in MDS patients.

Presentation Details

Presenter: Moshe Mittelman M.D.
Session: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Treatment Options and Decision Making in Low Risk MDS
Time: Saturday, December 9, 2023: 2:00 PM-3:30 PM
Location: Pacific Ballroom Salons 18-19 (Marriott Marquis San Diego Marina)
Abstract: Efficacy and Safety of Roxadustat for Treatment of Anemia in Patients with Lower-Risk Myelodysplastic Syndrome (LR-MDS) with Low Red Blood Cell (RBC) Transfusion Burden: Results of Phase III Matterhorn Study

About MATTERHORN
A total of one-hundred forty-one (141) subjects were enrolled in MATTERHORN (NCT03263091) a Phase 3, double-blind placebo-controlled study investigating the efficacy and safety of roxadustat for the treatment of anemia in patients with lower-risk transfusion-dependent myelodysplastic syndromes. The primary endpoint of the study is transfusion independence for ≥ 56 consecutive days in the first 28 weeks of treatment. The main secondary endpoint is the reduction of red blood cell transfusion.

About Myelodysplastic Syndromes Anemia

Myelodysplastic syndromes (MDS) are a group of disorders characterized by dysfunctional progenitor blood cells and stem cells, resulting in chronic anemia in most patients. Annual incidence rates of MDS are estimated to be 4.9/100,000 adults in the U.S1, thereof 77% are considered lower-risk MDS2. Approximately 80% of MDS patients have anemia at the time of diagnosis3 and around 60% of MDS patients will experience severe anemia (hemoglobin <8 g/dL) at some point during the course of their disease4. Anemia in MDS patients is associated with increased risk of cardiovascular complications and the need for blood transfusion5. Approximately 50% of patients with MDS require regular red blood cell transfusions6. Transfusion dependent MDS patients suffer higher rates of cardiac events, infections, iron overload with the related complications, and transformation to acute leukemia, associated with a decreased overall survival rate when compared with non-transfused patients with MDS, and decreased survival compared to an age-matched elderly population7. In addition, anemia frequently leads to significant fatigue, cognitive dysfunction, and decreased quality of life. There remains high unmet need for the treatment of anemia associated with MDS. Today, patients are routinely treated with erythropoiesis-stimulating agents (ESAs), luspatercept, or lenalidomide in lower-risk MDS with isolated del(5q), and hypomethylating agents (HMAs) in higher-risk disease8. Current anti-anemic agents are effective in about half of patients, with approximately 2 years duration of response9.

About Roxadustat
Roxadustat, an oral HIF-PH inhibitor that promotes erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improving iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA), and a Supplemental New Drug Application (sNDA) has been accepted by the China Health Authority.

Roxadustat is approved in China, Europe, Japan, and numerous other countries for the treatment of anemia of chronic kidney disease (CKD) in adult patients on dialysis (DD) and not on dialysis (NDD). Several other licensing applications for roxadustat have been submitted by partners, Astellas and AstraZeneca, to regulatory authorities across the globe. Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia, and the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen and AstraZeneca are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in markets not licensed to Astellas.

On December 9, 2023 Eisai (Headquarters: Tokyo, CEO: Haruo Naito) and Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada) reported that the Phase 3 LEAP-001 trial evaluating LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ, USA, did not meet its dual primary endpoints of overall survival (OS) and progression-free survival (PFS) for the first-line treatment of patients with advanced or recurrent endometrial carcinoma whose disease is mismatch repair proficient (pMMR)/not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) /MSI-H (Press release, Eisai, DEC 9, 2023, View Source [SID1234638323]).

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At the final analysis, KEYTRUDA plus LENVIMA did not improve OS or PFS sufficiently to meet the study’s prespecified statistical criteria in the first-line treatment of certain patients with advanced or recurrent endometrial carcinoma versus a standard of care, platinum-based chemotherapy doublet (carboplatin plus paclitaxel). The safety profile of LENVIMA plus KEYTRUDA was consistent with that observed in previously reported studies evaluating the combination. A full evaluation of the data from this study is ongoing. The companies will work with investigators to share the results with the scientific community.

"We remain confident in the proven benefit of KEYTRUDA plus LENVIMA for the treatment of appropriate patients with certain types of previously-treated advanced endometrial carcinoma based on results from the KEYNOTE-775/Study 309 trial and will continue to research the KEYTRUDA plus LENVIMA combination in patients with other types of difficult-to-treat cancers," said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck & Co., Inc., Rahway, NJ, USA Research Laboratories. "We are disappointed that the LEAP-001 trial did not-2-reach its primary endpoints, as we had hoped to bring another potential treatment option to patients when first diagnosed with certain types of advanced or recurrent endometrial carcinoma."

"Results from the LEAP-001 trial underscore the challenges of treating patients with advanced or recurrent endometrial carcinoma in the first-line setting," said Dr. Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead at Eisai Inc. "We remain optimistic about clinical development program for LENVIMA plus KEYTRUDA and are proud that the combination has become a standard of care option for patients with certain types of advanced or recurrent endometrial carcinoma whose disease has progressed following prior systemic therapy, and will continue our efforts to contribute to these patients. We are grateful to the patients, their loved ones, and the investigators whose participation is what makes scientific advancement possible."

LENVIMA plus KEYTRUDA is approved in the U.S., the EU, Japan and other countries for the treatment of certain types of advanced endometrial carcinoma following prior systemic therapy in any setting and advanced renal cell carcinoma (RCC). Lenvatinib is marketed as KISPLYX for advanced RCC in the EU. Eisai and Merck & Co., Inc., Rahway, NJ, USA are studying the LENVIMA plus KEYTRUDA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in various tumor types, including but not limited to hepatocellular carcinoma, RCC, head and neck cancer, gastric cancer and esophageal cancer, across multiple clinical trials. Results from the LEAP-001 trial do not affect the current approved indications for the KEYTRUDA plus LENVIMA combination or other ongoing trials from the LEAP clinical program.

About LEAP-001

LEAP-001 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT03884101) evaluating LENVIMA plus KEYTRUDA versus carboplatin plus paclitaxel for the first-line treatment of advanced or recurrent endometrial carcinoma. The dual primary endpoints are PFS, as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and OS. The secondary endpoints include objective response rate, as assessed by BICR per RECIST v1.1, quality of life measures, and safety. The study enrolled an estimated 842 patients who were randomized 1:1 to receive:  LENVIMA (20 mg orally once daily) plus KEYTRUDA (200 mg intravenously [IV] on Day 1 of each three-week cycle); or Paclitaxel (175 mg/m2 IV on Day 1 of each three-week cycle) plus carboplatin (IV infusion at a total dose of area-under-the-curve 6 [per Calvert’s formula] given on Day 1 of each three-week cycle).

About Endometrial Carcinoma

Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium and is the most common type of cancer in the uterus. Worldwide, it was estimated there were more than 417,000 new cases of uterine body cancer diagnosed and more than 97,000 deaths from the disease in 2020 (these estimates include both endometrial carcinomas and uterine sarcomas, more than 90% of uterine body cancers occur in the endometrium, so the actual numbers for endometrial carcinoma cases and deaths may be slightly lower than these estimates). In Japan, there were more than 17,000 new cases of uterine body cancer and more than 3,000 deaths from the disease in 2020.5 In the U.S., it is estimated there will be approximately 66,000 new cases of uterine body cancer diagnosed and approximately 13,000 deaths from the disease in 2023. In Europe, it is estimated there were more than 130,000 new cases of uterine body cancer and more than 29,000 deaths in 2020.3 The five-year relative survival rate for metastatic endometrial carcinoma (stage IV) is estimated to be approximately 20%.

About LENVIMA (lenvatinib) Capsules

LENVIMA, discovered and developed by Eisai, is an orally available multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, LENVIMA decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone. LENVIMA has been approved for the indications below.

Thyroid cancer

 Indication as monotherapy (Approved in over 80 countries including Japan, the United States, China, and countries in Europe and Asia) Japan: Unresectable thyroid cancer The United States: The treatment of patients with locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer (DTC) Europe: The treatment of adult patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine (RAI)

Hepatocellular carcinoma  Indication as monotherapy (Approved in over 80 countries including Japan, the United States, China, and countries in Europe and Asia) Japan: Unresectable hepatocellular carcinoma The United States: The first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) Europe: The treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy Thymic carcinoma  Indication as monotherapy (Approved in Japan) Japan: Unresectable thymic carcinoma

Renal cell carcinoma (In Europe, the agent was launched under the brand name Kisplyx)  Indication in combination with everolimus (Approved in over 65 countries including the United States, and countries in Europe and Asia) The United States: The treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy Europe: The treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor (VEGF) targeted therapy  Indication in combination with KEYTRUDA (generic name: pembrolizumab) (Approved in over 45 countries including Japan, the United States, and countries in Europe and Asia) Japan: Radically unresectable or metastatic renal cell carcinoma The United States: The first-line treatment of adult patients with advanced renal cell carcinoma Europe: The first-line treatment of adult patients with advanced renal cell carcinoma Endometrial carcinoma  Indication in combination with KEYTRUDA (Approved [including conditional approval] in over 50 countries including Japan, the United States, and countries in Europe and Asia) Japan: Unresectable, advanced or recurrent endometrial carcinoma that progressed after cancer chemotherapy The United States: The treatment of patients with advanced endometrial carcinoma (EC) that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation Europe: The treatment of adult patients with advanced or recurrent endometrial carcinoma (EC) who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and are not candidates for curative surgery

About KEYTRUDA (pembrolizumab) Injection, 100mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. Merck & Co., Inc., Rahway, NJ, USA has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.