On October 14, 2020 Dendreon Pharmaceuticals, a commercial-stage biopharmaceutical company and pioneer in the development of immunotherapy, reported publication of an analysis examining real-world survival outcomes in men with metastatic castrate-resistant prostate cancer (mCRPC) who were treated with PROVENGE (sipuleucel-T) and commonly prescribed oral treatments (Press release, Dendreon, OCT 14, 2020, View Source [SID1234568487]).

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The analysis of Medicare claims data from more than 6,000 fee-for-service beneficiaries showed that the addition of PROVENGE to either abiraterone acetate (Zytiga) or enzalutamide (Xtandi), at any point in a patient’s mCRPC treatment regimen, reduced the risk of death by 41% and prolonged median overall survival (OS) by 14.5 months.*

The analysis compared first-line treatment with PROVENGE versus first-line treatment with oral agents, including patients who received PROVENGE in the second-line or later, as well as any-line PROVENGE versus any-line oral agents (without PROVENGE), from 2013 to 2017. Findings were published online in the journal Advances in Therapy.1

"Based on our analysis, men with mCRPC who received sipuleucel-T had a significant improvement in median overall survival and reduction in the risk of death at three years, regardless of line of use," said Rana R. McKay, M.D., lead author and medical oncologist and assistant professor of medicine at Moores Cancer Center, University of California, San Diego. "These data contribute to a growing body of evidence demonstrating the real-world effectiveness of sipuleucel-T in the mCRPC patient."

Key findings of the analysis include:

In Medicare beneficiaries treated with approved mCRPC treatments, the median OS was significantly longer among men who also were treated with PROVENGE (35.2 months vs. 20.7 months in the any-line cohort and 34.9 months vs. 21.0 months in the first-line cohort).
Men who received PROVENGE as a first-line treatment had a 44% reduction in the risk of death at three years compared to those receiving oral agents as first-line treatment (adjusted hazard ratio, 0.56; 95% CI, 0.494-0.627). Similar results were observed in the any-line cohort, where there was a 41% decrease in the risk of death at three years in patients receiving PROVENGE versus those receiving an oral agent (without PROVENGE) (adjusted hazard ratio, 0.59; 95% CI, 0.527-0.651).
While safety was not a focus of this analysis, first-line use of PROVENGE resulted in fewer emergency department (ED) visits in the first year compared to oral treatments.
"This analysis underscores the importance of using complementary mechanisms of action to maximize patient survival outcomes and highlights the critical role immunotherapy plays in the modern era of mCRPC treatment," said Bruce A. Brown, M.D., chief medical officer at Dendreon. "PROVENGE continues to deliver on its promise of helping men with advanced prostate cancer live longer and should be considered when making treatment decisions in daily clinical practice."

Initial results from a univariate analysis of the data were presented in a poster session at the ASCO (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium in February 2020. The analysis was expanded to explore outcomes using a multivariable analysis to evaluate the impact of PROVENGE on overall survival.

About PROVENGE (sipuleucel-T)

PROVENGE is the only FDA-approved immunotherapy made from a patient’s own immune cells for the treatment of prostate cancer. Nearly 40,000 men have been prescribed PROVENGE, and it has been clinically proven to extend life for certain men in advanced stages of the disease.

INDICATION

PROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION

Acute Infusion Reactions: Acute infusion reactions (reported within 1 day of infusion) may occur and include nausea, vomiting, fatigue, fever, rigor or chills, respiratory events (dyspnea, hypoxia, and bronchospasm), syncope, hypotension, hypertension, and tachycardia.

Thromboembolic Events: Thromboembolic events, including deep venous thrombosis and pulmonary embolism, can occur following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. PROVENGE should be used with caution in patients with risk factors for thromboembolic events.

Vascular Disorders: Cerebrovascular events (hemorrhagic/ischemic strokes and transient ischemic attacks) and cardiovascular disorders (myocardial infarctions) have been reported following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.

Handling Precautions: PROVENGE is not tested for transmissible infectious diseases.

Concomitant Chemotherapy or Immunosuppressive Therapy: Chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied. Concurrent use of immune-suppressive agents may alter the efficacy and/or safety of PROVENGE.

Adverse Reactions: The most common adverse reactions reported in clinical trials (≥ 15% of patients receiving PROVENGE) were chills, fatigue, fever, back pain, nausea, joint ache, and headache.

On October 14, 2020 Broncus Holding Company ("Broncus"), a global leader in diagnostic and therapeutic technology for lung diseases, reported the closing of a Series C round of funding led by Lake Bleu Capital, and including Baidu Capital, the venture arm of one of the world’s largest Internet and data science companies, Ascendum Capital, CNCB Capital and DCP Capital, along with previous investor Qiming Venture Capital (Press release, Broncus Technologies, OCT 14, 2020, View Source [SID1234568486]).

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The funds will be used to further develop markets and technology across lung cancer, emphysema and other important lung diseases. Efforts will include expanding global market adoption of the Archimedes Virtual Bronchoscopic Navigation System combining Fused Fluoroscopy, real-time bronchoscopy and virtual bronchoscopic navigation for 3D views and access to nodules anywhere in the lungs; expanded commercial adoption and global clinical studies of the InterVapor System for Bronchoscopic Thermal Vapor Ablation (BTVA) used in emphysema; U.S. and European studies of the EMPOWER RF Catheter used in Bronchoscopic Radiofrequency Ablation (BRFA); and further development of next-generation RF technology to precisely treat lung nodules.

Broncus CEO Zhan Guowei said, "In recent years, medical device leaders such as Medtronic and Johnson & Johnson have invested in the market development of technologies for lung disease, which validates our forward-looking vision to focus exclusively on the diagnosis and treatment of diseases in the lung. Securing investors such as Lake Bleu Capital, Baidu Capital and Intuitive Surgical further supports our strategy to ‘own’ the lung when it comes to diagnosis and treatment. Our breakthrough navigation technology is enabling us to accelerate the development and commercialization of precise interventional technologies for diagnosis and treatment in order to improve options for patients with lung diseases and the physicians that care for them."

Dr. Li Bin, founder of Lake Bleu Capital, said: "Broncus is Lake Bleu’s major investment in the medical device sector this year because they are addressing a large and unmet need globally in the diagnosis and treatment of lung diseases. Their world-leading Archimedes lung navigation technology is supported with robust data and uniquely helps physicians accurately locate and reach targeted lesions, which will open the door to new and exciting interventional lung therapies. We believe that Broncus is well positioned to lead the world in providing less invasive methods to diagnose and treat lung disease broadly."

Broncus recently announced a new strategic partnership with Olympus Europa to exclusively distribute Broncus Medical’s Archimedes Planner and Archimedes Lite Virtual Bronchoscopic Navigation (VBN) system in several European countries.

Early investors in the company include Intuitive Surgical, an early pioneer and global technology leader in minimally invasive, robotic-assisted surgery.

On October 14, 2020 Bayer reported that the Phase III study CHRONOS-3 evaluating Aliqopa (copanlisib) in combination with rituximab in indolent Non-Hodgkin’s Lymphoma (iNHL) patients (n=458) who have relapsed after one or more prior lines of rituximab-containing therapy has met its primary endpoint of prolonged progression-free survival (PFS) (Press release, Bayer, OCT 14, 2020, View Source [SID1234568485]). The study predominantly included patients with follicular lymphoma (FL) and marginal zone lymphoma, as well as patients with small lymphocytic lymphoma and lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. In 2017, based on the Phase II CHRONOS-1 study, Aliqopa was approved for the treatment of adult patients with relapsed FL who have received at least two prior systemic therapies. Accelerated approval was granted for this indication based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

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"The positive results from CHRONOS-3 demonstrate the potential clinical benefit of copanlisib in combination with rituximab, to address the unmet medical need in these patients."

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CHRONOS-3 is a Phase III randomized, double-blind, placebo-controlled trial with the objective to evaluate whether Aliqopa in combination with rituximab is superior to placebo plus rituximab in extending PFS in patients with relapsed iNHL following at least one prior rituximab product. The safety observed in the trial was generally consistent with previously published data on the individual components of the combination and no new safety signals were identified.

"Indolent forms of Non-Hodgkin’s Lymphoma are a heterogenous group of malignancies characterized by a chronic pattern of remissions and recurrences. For iNHL patients with disease progression who are in need of treatment, there are few approved treatment options," said Dr. Scott Z. Fields, Senior Vice President and Head of Oncology Development at Bayer. "The positive results from CHRONOS-3 demonstrate the potential clinical benefit of copanlisib in combination with rituximab, to address the unmet medical need in these patients."

Results from CHRONOS-3 will be presented at a scientific congress. Bayer plans to discuss the data from CHRONOS-3 with health authorities worldwide.

Aliqopa is an intravenous phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant activity against alpha and delta isoforms the PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells.i Aliqopa is approved in the U.S. under the accelerated approval pathway for the treatment of adult patients with relapsed FL who have received at least two prior systemic therapies. Accelerated approval was granted for this indication based on an ORR of 59% (n=61) 95% CI: 49, 68, including 14% (15/104) of complete responses (CRs) from the open-label, single-arm multicenter, Phase II clinical trial (CHRONOS-1), in a total of 142 subjects, which included 104 subjects with follicular B-cell non-Hodgkin lymphoma who had relapsed disease following at least two prior treatments. In the updated two-year follow-up analysis, Aliqopa ORR was 59% (n=61) 95% CI: 49, 68, including 20% CR (n=21).ii Tumor response was assessed according to the International Working Group response criteria for malignant lymphoma. Efficacy based on ORR was assessed by an Independent Review Committee. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial.

About CHRONOS-3

CHRONOS-3 is a Phase III randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Aliqopa in combination with rituximab versus placebo in combination with rituximab in patients with relapsed indolent NHL who have received at least one or more lines of prior rituximab-containing treatment. Histological subtypes included in the trial were follicular lymphoma (FL), small lymphocytic lymphoma (SLL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), and marginal zone lymphoma (MZL). Patients must have relapsed after the last rituximab- containing therapy and either had a treatment-free interval of ≥ 12 months after completion of the last rituximab-containing treatment, or are unwilling to receive chemotherapy or for whom chemotherapy is contraindicated on reason of age, comorbidities, and/or residual toxicity (NCT02367040). The study enrolled 458 participants.

About Non-Hodgkin’s Lymphoma

Non-Hodgkin’s Lymphoma (NHL) comprises a highly heterogeneous group of chronic diseases with poor prognosis. NHL is the most common hematologic malignancy and the tenth most common cancer worldwide, with nearly 510,000 new cases diagnosed in 2018. It accounts for nearly 249,000 deaths worldwide in 2018.

Indolent NHL consists of multiple subtypes, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM). While the disease is typically slowly growing, it can become more aggressive over time. Despite treatment advances, there remains a need for improved treatment options for the relapsed or refractory stage of the disease. After response to initial therapy, response rates and duration of response decline with subsequent lines of therapy, underscoring the need for patients whose disease has already progressed.

About Aliqopa (copanlisib) Injection

Aliqopa (copanlisib) is indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies. Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Aliqopa is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3K-α and PI3K-δ isoforms expressed in malignant B cells. Aliqopa has been shown to induce tumor cell death by apoptosis and inhibition of proliferation of primary malignant B cell lines. Aliqopa inhibits several key cell-signaling pathways, including B-cell receptor signaling, CXCR12 mediated chemotaxis of malignant B cells, and NFκB signaling in lymphoma cell lines.

IMPORTANT SAFETY INFORMATION

Infections: Serious, including fatal, infections occurred in 19% of 317 patients treated with ALIQOPA monotherapy. The most common serious infection was pneumonia. Monitor patients for signs and symptoms of infection and withhold ALIQOPA for Grade 3 and higher infection.

Serious pneumocystis jiroveci pneumonia (PJP) infection occurred in 0.6% of 317 patients treated with ALIQOPA monotherapy. Before initiating treatment with ALIQOPA, consider PJP prophylaxis for populations at risk. Withhold ALIQOPA in patients with suspected PJP infection of any grade. If confirmed, treat infection until resolution, then resume ALIQOPA at previous dose with concomitant PJP prophylaxis.

Hyperglycemia: Grade 3 or 4 hyperglycemia (blood glucose 250 mg/dL or greater) occurred in 41% of 317 patients treated with ALIQOPA monotherapy. Serious hyperglycemic events occurred in 2.8% of patients. Treatment with ALIQOPA may result in infusion-related hyperglycemia. Blood glucose levels typically peaked 5 to 8 hours post-infusion and subsequently declined to baseline levels for a majority of patients; blood glucose levels remained elevated in 17.7% of patients one day after ALIQOPA infusion. Of 155 patients with baseline HbA1c <5.7%, 16 (10%) patients had HbA1c >6.5% at the end of treatment.

Of the twenty patients with diabetes mellitus treated in CHRONOS-1, seven developed Grade 4 hyperglycemia and two discontinued treatment. Patients with diabetes mellitus should only be treated with ALIQOPA following adequate glucose control and should be monitored closely.

Achieve optimal blood glucose control before starting each ALIQOPA infusion. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of hyperglycemia.

Hypertension: Grade 3 hypertension (systolic 160 mmHg or greater or diastolic 100 mmHg or greater) occurred in 26% of 317 patients treated with ALIQOPA monotherapy. Serious hypertensive events occurred in 0.9% of 317 patients. Treatment with ALIQOPA may result in infusion-related hypertension. The mean change of systolic and diastolic BP from baseline to 2 hours post-infusion on Cycle 1 Day 1 was 16.8 mmHg and 7.8 mmHg, respectively. The mean BP started decreasing approximately 2 hours post-infusion; BP remained elevated for 6 to 8 hours after the start of the ALIQOPA infusion. Optimal BP control should be achieved before starting each ALIQOPA infusion. Monitor BP pre- and post-infusion. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of hypertension.

Non-infectious Pneumonitis: Non-infectious pneumonitis occurred in 5% of 317 patients treated with ALIQOPA monotherapy. Withhold ALIQOPA and conduct a diagnostic examination of a patient who is experiencing pulmonary symptoms such as cough, dyspnea, hypoxia, or interstitial infiltrates on radiologic exam. Patients with pneumonitis thought to be caused by ALIQOPA have been managed by withholding ALIQOPA and administration of systemic corticosteroids. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of non-infectious pneumonitis.

Neutropenia: Grade 3 or 4 neutropenia occurred in 24% of 317 patients treated with ALIQOPA monotherapy. Serious neutropenic events occurred in 1.3%. Monitor blood counts at least weekly during treatment with ALIQOPA. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of neutropenia.

Severe Cutaneous Reaction: Grade 3 and 4 cutaneous reactions occurred in 2.8% and 0.6% of 317 patients treated with ALIQOPA monotherapy respectively. Serious cutaneous reaction events were reported in 0.9%. The reported events included dermatitis exfoliative, exfoliative rash, pruritus, and rash (including maculo-papular rash). Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of severe cutaneous reactions.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ALIQOPA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of copanlisib to pregnant rats during organogenesis caused embryo-fetal death and fetal abnormalities in rats at maternal doses as low as 0.75 mg/kg/day (4.5 mg/m2/day body surface area) corresponding to approximately 12% the recommended dose for patients. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least one month after the last dose.

Adverse Drug Reactions: Serious adverse reactions were reported in 44 (26%) patients. The most frequent serious adverse reactions that occurred were pneumonia (8%), pneumonitis (5%) and hyperglycemia (5%). Adverse reactions resulted in dose reduction in 36 (21%) and discontinuation in 27 (16%) patients. The most frequently observed adverse drug reactions (≥20%) in ALIQOPA-treated patients were: hyperglycemia (54%), leukopenia (36%), diarrhea (36%), decreased general strength and energy (36%), hypertension (35%), neutropenia (32%), nausea (26%), thrombocytopenia (22%), and lower respiratory tract infections (21%).

Drug Interactions: Avoid concomitant use with strong CYP3A inducers. Reduce the ALIQOPA dose to 45 mg when concomitantly administered with strong CYP3A inhibitors.

Lactation: Advise women not to breastfeed. Advise a lactating woman not to breastfeed during treatment with ALIQOPA and for at least 1 month after the last dose.

For important risk and use information about Aliqopa, please see the full Prescribing Information.

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products across various indications and several compounds in different stages of clinical development. The company’s approach to research prioritizes targets and pathways with the potential to impact the way cancer is treated.

On October 14, 2020 Astex Pharmaceuticals, Inc., a member of the Otsuka group of companies, and Otsuka Pharmaceutical Co., Ltd., reported top-line results of the ASTRAL-2 and ASTRAL-3 clinical studies that evaluated the efficacy and safety of guadecitabine (SGI-110) in adults with previously treated AML (ASTRAL-2), and with previously treated MDS/CMML (ASTRAL-3), respectively (Press release, Astex Pharmaceuticals, OCT 14, 2020, View Source [SID1234568484]). Neither study met the primary endpoint of statistically significant (p <0.05) improvement in overall survival (OS) compared with the control arm of physicians’ choice of alternative therapy. Evaluation of the studies’ prospective subgroups and secondary endpoints is ongoing. Safety data were consistent with the expected safety profile of guadecitabine from prior studies. The full data will be presented at upcoming scientific meetings.

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"We are disappointed in the outcome of the ASTRAL-2 and ASTRAL-3 studies," said Mohammad Azab, Astex’s president and chief medical officer. "The ASTRAL series of studies were designed to deliver a new therapeutic option to patients with AML or MDS/CMML, and although guadecitabine is an active drug, the studies failed to demonstrate a statistically superior survival outcome compared to current therapeutic alternatives." Dr. Azab also added, "The ASTRAL studies generated for the medical community one of the largest bodies of clinical and genetic data from prospective randomized studies using hypomethylating agent (HMA) treatment. Guadecitabine was associated with improved outcomes in certain subgroups, but that needs to be validated by additional studies. We are extremely grateful to all the patients, physicians and other healthcare professionals, and collaborating research and manufacturing organizations who contributed to this global effort."

Guadecitabine is an investigational compound and is not currently approved in any country.

About Guadecitabine

Guadecitabine is a next-generation DNA hypomethylating agent.1,2 Guadecitabine was rationally designed to be resistant to degradation by cytidine deaminase, prolonging the exposure of tumor cells to the active metabolite, decitabine, thus ensuring greater uptake of decitabine into the DNA of rapidly dividing cancer cells.3 Guadecitabine, through the action of decitabine, inhibits DNA methyl transferase (DNMT), with the potential to reverse aberrant DNA methylation, an epigenetic change characteristic of many cancer cells, and may restore the expression of silenced tumor suppressor genes and tumor-associated antigens.4 Through this re-expression of silenced genes, guadecitabine may have the potential to sensitize tumor cells to other anticancer agents,5,6,7 including immunotherapeutics,8 as well as re-sensitizing cancer cells previously resistant to chemotherapeutics.7

Guadecitabine was designed to be administered subcutaneously as a low-volume, stable formulation.

Astex and Otsuka announced in July 2018 that the global phase 3 ASTRAL-1 randomized study of guadecitabine in adults with previously untreated AML who were not eligible for intensive induction chemotherapy (View Source NCT02348489) failed to meet its co-primary endpoints.

Guadecitabine is also being evaluated in over twenty investigator-sponsored trials in other hematological malignancies and in solid tumors, both as a single agent and in combination with chemotherapy or immunotherapy.

About the ASTRAL-2 Study

The ASTRAL-2 study (View Source NCT02920008) evaluated the efficacy and safety of guadecitabine in adults with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who were refractory to initial induction (primary refractory) or in relapse after such initial induction with or without prior hematopoietic cell transplantation. The study randomized 302 patients from 98 investigator sites in 15 countries worldwide. The study randomized patients 1:1 to receive in 28-day cycles either guadecitabine, delivered subcutaneously for 10 days in Cycle 1 followed by 10 or 5 days in Cycle 2, and 5 days in Cycle 3 onwards, or physicians’ choice of (i) a high intensity regimen comprising intermediate or high dose cytarabine; mitoxantrone, etoposide, and cytarabine (MEC); or fludarabine, cytarabine, G-CSF, +/- idarubicin (FLAG/FLAG-Ida); (ii) a low intensity regimen comprising low dose cytarabine or azacitidine or decitabine; and (iii) Best Supportive Care only. In addition to the primary endpoint of OS, the study evaluated multiple secondary endpoints including event-free survival, long-term survival, number of days alive and out of the hospital, disease response, transfusion independence rate, complete response rate, composite complete response, hematopoietic cell transplant rate, duration of complete response, quality of life, incidence and severity of adverse events, and 30-day and 60-day all-cause mortality.

About the ASTRAL-3 Study

The ASTRAL-3 study (View Source NCT02907359) evaluated the efficacy and safety of guadecitabine in adults with MDS or CMML previously treated with a hypomethylating agent. The study randomized 417 patients from 91 investigator sites in 14 countries worldwide. The study randomized patients 2:1 to receive in 28-day cycles either guadecitabine delivered subcutaneously for 5 days, or physicians’ choice of (i) low dose cytarabine; (ii) a standard intensive chemotherapy (IC) 7+3 regimen of cytarabine and an anthracycline, or mitoxantrone; and (iii) Best Supportive Care only. In addition to the primary endpoint of OS, the study evaluated multiple secondary endpoints including transfusion independence, marrow complete response rate, survival rate, leukemia-free survival, number of days alive and out of the hospital, disease response, duration of response, number of transfusions, health-related quality of life, incidence and severity of adverse events, and 30-day and 60-day all-cause mortality.

About Acute Myeloid Leukemia

AML is the most common form of acute leukemia in adults.9 An estimated 19,940 new cases of AML are projected in the U.S. in 2020,10 and an estimate of 11,180 patients are projected to die from AML in the U.S. in 2020.10 Although 60 to 80 percent of AML patients less than 60 years of age may achieve a complete response with standard intensive induction chemotherapy,11 the outlook for previously treated patients, and for patients 60 years of age or more, particularly those with comorbidities, is significantly worse, and these patients are in need of effective, less toxic therapies.

About Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia

Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. U.S. incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.12,13 The prevalence has been estimated to be from 60,000 to 170,000 in the U.S.14 MDS may evolve into acute myeloid leukemia in one-third of patients.15 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML.

CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the U.S. is approximately 1,100 new cases per year,16 and CMML may transform into AML in 15% to 30% of patients.17

The hypomethylating agents decitabine, azacitidine, and oral decitabine and cedazuridine are FDA-approved for the treatment of intermediate and high-risk MDS and CMML.18,19,20 There is no approved therapy for patients who fail treatment with hypomethylating agents, and median survival following failure is less than six months.21

On October 14, 2020 Genmab A/S (Nasdaq: GMAB) reported that multiple abstracts for Genmab programs were accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting (Press release, Genmab, OCT 14, 2020, View Source [SID1234568483]). Accepted abstracts include preliminary data from the first-in-human Phase 1/2a study of DuoBody-PD-L1x4-1BB (GEN1046), a bispecific antibody in joint development with BioNTech, in patients with advanced solid tumors, which was accepted for e-poster presentation. All abstracts are scheduled to be available on the SITC (Free SITC Whitepaper) website on November 9, 2020.

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"We are pleased that the first clinical data for DuoBody-PD-L1x4-1BB (GEN1046), which we are developing in collaboration with BioNTech, was selected for presentation at the SITC (Free SITC Whitepaper) 35th Anniversary Annual Meeting," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "The preliminary Phase 1/2a data demonstrate the potential of DuoBody-PD-L1x4-1BB (GEN1046) in solid tumors and we look forward to this first data being shared with the medical community."

Abstracts

DuoBody-PD-L1x4-1BB (GEN1046)1:
First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody-PD L1×4-1BB (GEN1046) in patients with advanced solid tumors – e-poster presentation, available in the virtual poster hall from November 11 – 14, 2020.

DuoBody-PD-L1×4-1BB (GEN1046) induces superior immune-cell activation, cytokine production and cytotoxicity by combining PD-L1 blockade with conditional 4-1BB co-stimulation – e-poster presentation, available in the virtual poster hall from November 11 – 14, 2020.

Tisotumab vedotin2:
Tisotumab vedotin shows immunomodulatory activity through induction of immunogenic cell death – e-poster presentation, available in the virtual poster hall from November 11 – 14, 2020.

DuoBody-CD3x5T43:
Pre-clinical mechanism of action and pharmacodynamic biomarker studies of DuoBody-CD3x5T4 in vitro and in vivo in solid cancer models – e-poster presentation, available in the virtual poster hall from November 11 – 14, 2020.

Non-asset specific:
Molecular dissection of tumor-immune microenvironment factors associated with response to checkpoint inhibitor therapy in non-small cell lung cancer patients using Nanostring Digital Spatial Profiling – e-poster presentation, available in the virtual poster hall from November 11 – 14, 2020.