On May 19, 2021 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported additional clinical data for lifileucel alone and in combination with pembrolizumab in patients with advanced melanoma (Press release, Iovance Biotherapeutics, MAY 19, 2021, View Source [SID1234580279]). The data are available in two ASCO (Free ASCO Whitepaper) abstracts, with additional updates to be provided at the upcoming ASCO (Free ASCO Whitepaper) 2021 Annual Meeting, to be held June 4-8, 2021 .

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Maria Fardis, Ph.D., President and Chief Executive Officer of Iovance Biotherapeutics, stated, "We are very excited that our latest clinical datasets demonstrate the broad potential for lifileucel in advanced melanoma. For the first time we are reporting results for lifileucel as an earlier treatment for advanced melanoma in combination with pembrolizumab, demonstrating an overall response rate (ORR) of 86% in patients who are naïve to anti-PD-1 therapy. We are impressed with the results for this combination regimen, particularly since pembrolizumab alone demonstrated a 33% ORR in a comparable patient population. In addition, in a post-PD1 advanced melanoma patient population in Cohort 2 in the C-144-01 study, shorter duration of prior anti-PD-1 therapy maximizes Duration of Response (DOR) to lifileucel treatment."

Lifileucel in Combination with Pembrolizumab in Advanced Melanoma (IOV-COM-202 Study)
Early data suggest the response rate of lifileucel plus pembrolizumab may be additive in patients with immune checkpoint inhibitor (ICI)-naïve advanced melanoma. Cohort 1A in the IOV-COM-202 study is evaluating lifileucel in combination with pembrolizumab in up to 12 patients who are naïve to ICI, or anti-PD-1, therapy. Six of the initial seven patients had a confirmed objective response, representing an 86% ORR (1 Complete Response (CR) and 5 Partial Responses (PR), with one best response of stable disease (abstract data extraction: February 2021). The longest duration of response was 16.8 months.

The Treatment-Emergent Adverse Event (TEAE) profile was consistent with the underlying disease and known Adverse Event (AE) profiles of pembrolizumab, NMA-LD and IL-2. These encouraging data confirm the potential feasibility and activity of lifileucel in combination with pembrolizumab in early-line treatment of patients with advanced melanoma. Updated results for the initial seven patients will be available in the upcoming ASCO (Free ASCO Whitepaper) poster.

Lifileucel Following anti-PD-1 therapy in Advanced Melanoma (C-144-01 clinical study)
As previously reported, the long-term follow-up data for Cohort 2 in the C-144-01 clinical study continue to demonstrate durability and depth of lifileucel TIL therapy response. DOR was not reached at 28.1 months of median study follow up and ORR remained at 36.4 percent.

New data in the ASCO (Free ASCO Whitepaper) abstract suggest that DOR was positively associated with shorter cumulative duration of prior anti-PD-1 therapy. In responders, the median cumulative duration and median prior lines of anti-PD-1 therapy was 4.4 months (range: 1.4-22.5 months) and 1.5 lines (range: 1-4). These results support earlier use of lifileucel following anti-PD-1 therapy instead of retreatment with anti-PD-1 based – regimens.

All patients in Cohort 2 had high baseline disease burden and were heavily pretreated (3.3 mean prior therapies), including anti-PD1 and BRAF/MEK inhibitors if BRAFV600 mutation positive. The adverse event profile was consistent with the underlying advanced disease, lymphodepletion and IL-2 regimens, with no new adverse events emerging over time. Updated results for Cohort 2 with longer duration of follow up will be part of the oral presentation during ASCO (Free ASCO Whitepaper) 2021.

Iovance Presentation and Poster at ASCO (Free ASCO Whitepaper) 2021

Title: Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy.
Authors: James M. G. Larkin, et al.
Session Title: Melanoma/Skin Cancers
Session Type: Oral Abstract Session
Abstract Number: 9505
Location: ASCO (Free ASCO Whitepaper) Meeting Library at View Source and View Source
Session Date and Time: Sunday, June 6, 2021 from 8:00 – 11:00 a.m. ET

Title: Safety and efficacy of lifileucel (LN-144), an autologous, tumor infiltrating lymphocyte cell therapy in combination with pembrolizumab for immune checkpoint inhibitor naïve patients with advanced melanoma.
Authors: Sajeve Samuel Thomas, et al.
Session Title: Melanoma/Skin Cancers
Session Type: ePoster Session
Abstract Number: 9537
Location: ASCO (Free ASCO Whitepaper) Meeting Library at View Source and View Source
ePoster Viewing: on demand beginning Friday, June 4, 2021 at 9:00 a.m. ET

On May 19, 2021 Sensei Biotherapeutics, a clinical-stage immunotherapy company focused on the discovery and development of next generation therapeutics for cancer, reported new data from the ongoing Phase 1/2 clinical trial of SNS-301, an investigational medicine in patients with advanced squamous cell carcinoma of the head and neck (SCCHN), in combination with pembrolizumab (Press release, Sensei Biotherapeutics, MAY 19, 2021, View Source [SID1234580278]). The data will be presented as a poster by Alain Algazi, M.D., from the University of California San Francisco to the medical community at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place virtually June 4 – 8, 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As of the April 14, 2021 cut-off date, 21 patients with locally advanced unresectable or metastatic SCCHN had been enrolled and treated in the study. Twenty of the patients enrolled did not achieve an objective response to prior treatment with PD-1 blockade (Cohort A) and one patient was PD-1 blockade naïve (Cohort B). The safety profile of SNS-301 in combination with pembrolizumab observed from 20 evaluable patients was favorable and consistent with previously reported data. Efficacy data was available from twelve patients in Cohort A. Notably, the efficacy bar was set high by enrolling patients with no objective response to prior PD-1 blockade (median 7.5 months). Data from nine evaluable patients from Cohort A were last reported from this study at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 35th Annual Meeting.

"These data suggest SNS-301, when combined with PD-1 blockade, has the potential to provide long-term benefit as second and later line treatment for patients with late-stage cancer and few other treatment options," said Marie-Louise Fjallskog, M.D., Ph.D., Chief Medical Officer of Sensei Biotherapeutics. "We expect to report more mature data, including data for SNS-301 combination therapy in the frontline setting, by the end of this year."

"This study continues to enhance our understanding of the broad potential of our ImmunoPhage platform," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "The information we are gathering is just one aspect of the potential of our ImmunoPhage platform to expand the durability and improve the treatment of many devastating cancers. Our team continues to lead advances in the understanding of bacteriophage through internal research and collaborations with world-class academic laboratories, and we are excited to apply these learnings to our pipeline of ImmunoPhage programs."

Data from Phase 1/2 Trial of SNS-301 SSCCHN As of April 14, 2021

Data highlighted today are part of a poster (#6029), titled: "Update on Safety and Efficacy of a Phase 1/2 Trial of SNS-301 and Pembrolizumab in Patients with Advanced Squamous Cell Carcinoma of the Head and Neck." The abstract and related poster can be downloaded from the ASCO (Free ASCO Whitepaper) Meeting Library.

Safety Data

As of the data cut-off, a safety analysis conducted in 20 evaluable patients showed that SNS-301 in combination with pembrolizumab continues to have a favorable safety profile.

The combination of SNS-301 and pembrolizumab was well tolerated. Mostly Grade 1-2, mild to moderate, unrelated adverse events (AE) were observed. Four Grade 3 AEs were reported as treatment-related: dehydration, pruritus, rash and EKG QT prolongation.
Efficacy Data

An analysis of anti-tumor activity was conducted in 12 patients who did not achieve an objective response to prior treatment with PD-1 blockade (Cohort A). No patients were evaluable from Cohort B as of the cut-off date.

67% (n=8/12) of patients achieved stable disease (SD) or partial response (PR), including:
One patient with PD-L1 negative tumor who achieved a tumor reduction of 71% that is still ongoing after 11 months of therapy. Nanostring data for this patient show T-cell increase and T-cell activation.
Seven patients achieved SD, including two patients with long-standing SD (8 and 10 months).
Patient outcomes appear to correlate to post-treatment PD-L1 expression and immune infiltration in tumors.

Analyses of secondary endpoints using ELISA and ELISPOT assays to evaluate SNS-301 specific B and T cell responses in patient samples are ongoing. Sensei expects to report these data as part of the larger dataset planned by the end of 2021. Sensei also plans to add a third cohort by the end of 2021 to evaluate SNS-301 with HPV-specific E6/E7 ImmunoPhage.

About the Phase 1/2 Clinical Study

The multi-center Phase 1/2 clinical trial is designed to evaluate safety, tolerability, and anti-tumor activity of SNS-301 in combination with pembrolizumab, as well as immune response and tumor/immune biomarkers. The study has two cohorts with a total of 60 patients with locally advanced unresectable or metastatic squamous cell carcinoma of the head and neck (SCCHN) who did not achieve a response to prior treatment with PD-1 blockade (Cohort A) or patients who did not receive prior therapy with PD-1 blockade (Cohort B).

About ImmunoPhage Platform

Sensei’s proprietary ImmunoPhage platform enables the delivery of innovative treatments that are personalized to a patient’s own tumor specific antigens. Bacteriophages have built-in capabilities that utilize the inherent nature of viruses to elicit the innate and adaptive immune system, supporting a highly immunogenic approach. SNS-301 is a first-in-class and self-adjuvanted bacteriophage-base immune-activating vaccine targeting human aspartate β-hydroxylase (ASPH), a tumor-associated antigen commonly overexpressed in cancer.

About SNS-301

SNS-301 is a first-in-class cancer immunotherapy designed to overcome immune tolerance and induce robust and durable antigen-specific humoral and cellular responses. It is a bio-engineered, inactivated bacteriophage virus expressing a fragment of the tumor-associated antigen, ASPH, as a fusion protein to the bacteriophage lambda capsid decoration protein, gpD. Expression of ASPH is uniquely upregulated in more than 20 different types of cancer and expression levels in various tumors are generally inversely correlated with disease prognosis. ASPH signaling is related to cancer cell growth, cell motility and invasiveness, occurs through the Notch pathway and is implicated in the epithelial to mesenchymal transition (EMT).

On May 19, 2021 MorphoSys AG (FSE:MOR; NASDAQ:MOR) reported that new data from the tafasitamab (Monjuvi(R)) development program will be presented at the upcoming 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 4-8, 2021 (Press release, MorphoSys, MAY 19, 2021, View Source [SID1234580277]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody, which was approved as Monjuvi(R) (tafasitamab-cxix) in July 2020 by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

"We are proud to present important findings from our comprehensive development program for tafasitamab at the ASCO (Free ASCO Whitepaper) Annual Meeting, including three-year follow-up data from the Phase 2 L-MIND study showing a long durability of responses and overall survival in patients with R/R DLBCL," commented Dr. Malte Peters, Chief Research and Development Officer at MorphoSys. "In addition, we will show details from our First-MIND study in front-line DLBCL, indicating our ambition to position Monjuvi as a back-bone strategy in DLBCL and to increase cure rates or duration of remission in DLBCL across all lines of therapy."

Abstracts accepted for presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting include:

Poster Discussion

LONG-TERM ANALYSES FROM L-MIND, A PHASE 2 STUDY OF TAFASITAMAB (MOR208) COMBINED WITH LENALIDOMIDE (LEN) IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (R/R DLBCL)

Abstract Number: 7513
Session: Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia

ePosters

First-MIND: A PHASE 1B, OPEN-LABEL, RANDOMIZED STUDY TO ASSESS SAFETY OF TAFASITAMAB (TAFA) OR TAFA + LENALIDOMIDE (LEN) IN ADDITION TO R‑CHOP IN PATIENTS WITH NEWLY DIAGNOSED DLBCL

Abstract Number: 7540
Session: Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia

A PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TAFASITAMAB PLUS LENALIDOMIDE AND RITUXIMAB VERSUS PLACEBO PLUS LENALIDOMIDE AND RITUXIMAB IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL) OR MARGINAL ZONE LYMPHOMA (MZL)[1]

Abstract Number: TPS7568
Session: Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia

Please refer to the ASCO (Free ASCO Whitepaper) online program for full session details and data presentation listings: View Source All presentations will be available on demand starting June 4, 2021.

MorphoSys is looking forward to meeting registered ASCO (Free ASCO Whitepaper)21 Virtual attendees at its virtual booth accessible through the conference website and through the company’s ASCO (Free ASCO Whitepaper) microsite at www.morphosysevents.com.

About Tafasitamab
Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb(R) engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Monjuvi(R) (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. Monjuvi(R) is being co-commercialized by Incyte and MorphoSys in the United States. Incyte has exclusive commercialization rights outside the United States.

A marketing authorization application (MAA) seeking the approval of tafasitamab in combination with lenalidomide in the EU has been validated by the European Medicines Agency (EMA) and is currently under review for the treatment of adult patients with relapsed or refractory DLBCL, including DLBCL arising from low grade lymphoma, who are not candidates for ASCT.

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in a number of ongoing combination trials.

Monjuvi(R) is a registered trademark of MorphoSys AG.

XmAb(R) is a registered trademark of Xencor, Inc.

Important Safety Information

What are the possible side effects of MONJUVI?

MONJUVI may cause serious side effects, including:

– Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get chills, flushing, headache, or shortness of breath during an infusion of MONJUVI.

– Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or any bruising or bleeding.

– Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or develop any signs and symptoms of an infection.

The most common side effects of MONJUVI include:

– Feeling tired or weak

– Diarrhea

– Cough

– Fever

– Swelling of lower legs or hands

– Respiratory tract infection

– Decreased appetite

These are not all the possible side effects of MONJUVI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you:

– Have an active infection or have had one recently.

– Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.

– You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.

– Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.

– Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.

You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

On May 19, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, reported the presentation of additional data from the Phase 3 TIVO-3 study comparing FOTIVDA (tivozanib) to sorafenib in relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies (Press release, AVEO, MAY 19, 2021, View Source [SID1234580276]). The data, which includes updated durability of response (DOR) and overall survival (OS) results, as well as an analysis of treatment-emergent adverse events (TEAEs) across study arms, will be featured in two poster presentations at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 4-8 in a virtual setting. FOTIVDA, AVEO’s oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI), is approved by the U.S. Food and Drug Administration for the treatment of adults with relapsed or refractory advanced RCC following two or more prior systemic therapies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"With advances in RCC treatment, patients are living longer, increasing the need for proven, well tolerated options in the relapsed or refractory setting," said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial. "The TIVO-3 study is the first positive Phase 3 study in RCC patients who received two or more prior systemic therapies, and these long-term follow up results continue to demonstrate the depth and durability of responses to FOTIVDA, as well as a tolerability profile that is particularly important in the later-stage treatment setting."

"FOTIVDA has demonstrated a differentiated clinical profile, and we are very pleased with initial receptivity to this differentiation and to the importance of the unique dataset that the TIVO-3 study represents in the commercial setting," said Michael Bailey, president and chief executive officer of AVEO. "We were also pleased to see efficacy advantages relative to sorafenib were maintained or improved with longer follow-up. We look forward to continuing to elucidate FOTIVDA’s potential in the clinic, particularly in the immunotherapy combination setting, with patient enrollment in the pivotal Phase 3 TiNivo-2 study of FOTIVDA in combination with OPDIVO (nivolumab) anticipated to commence mid-year and execution of the Phase 2 hepatocellular carcinoma DEDUCTIVE trial in combination with IMFINZI (durvalumab) ongoing."

TIVO-3 ASCO (Free ASCO Whitepaper) Data

TIVO-3 is a Phase 3, open-label study that enrolled patients with metastatic RCC whose disease progressed on two or more prior systemic regimens, one of which included a VEGFR TKI. Patients were stratified by International Metastatic RCC Database Consortium (IMDC) risk category (favorable, intermediate, or poor) and type of prior therapy (two prior VEGFR TKIs, VEGFR TKI plus checkpoint inhibitor, VEGFR TKI plus any other systemic agent) then randomized 1:1 to receive tivozanib or sorafenib. Results from the study were published in Lancet Oncology (December 2019). Additional analyses and long-term follow up results from the TIVO-3 study to be presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting include:

Durability of Response and Updated Overall Survival. Tivozanib demonstrated clinically meaningful and statistically significant improvements in overall response rate (ORR) and DOR compared to sorafenib in 350 patients randomized 1:1 with highly relapsed or refractory RCC. As of a January 15, 2021 data cutoff date, the median DOR for patients treated with tivozanib was 20.3 months (95% CI, 9.8-29.9 months) compared to 9.0 months (95% CI, 3.7-16.6 months) for patients treated with sorafenib. The ORR for patients treated with tivozanib was 23% compared to 11% for patients treated with sorafenib. Furthermore, long-term OS relative to sorafenib continues to improve (hazard ratio (HR): 0.91 [95% CI, 0.716-1.165; p=0.47]). The OS HR assesses the relative risk of death for the entirety of the data set.
Temporal Characteristics of Treatment-Emergent Adverse Events and Dose Modifications. Patients in the TIVO-3 study had longer duration of treatment exposure with tivozanib than sorafenib (11.9 cycles vs. 6.7 cycles), but fewer all-grade and grade ≥3 TEAEs. TEAEs were generally similar with tivozanib and sorafenib. Time to dose modifications was longer with tivozanib than sorafenib. Among those with the same TEAEs, dose reductions, interruptions, or discontinuations were required more frequently with sorafenib than tivozanib.
A copy of each poster will be available at www.aveooncology.com after its presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

ASCO Presentation Details

Title: TIVO-3: Durability of response and updated overall survival of tivozanib versus sorafenib in metastatic renal cell carcinoma (mRCC).
Abstract: 4546
Track: Genitourinary Cancer—Kidney and Bladder
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
Title: Temporal characteristics of treatment-emergent adverse events and dose modifications with tivozanib and sorafenib in the Phase 3 TIVO-3 study of relapsed or refractory mRCC.
Abstract: 4567
Track: Genitourinary Cancer—Kidney and Bladder
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.1 FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.

Females and Males of Reproductive Potential: Can impair fertility.

Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.FOTIVDA.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.2 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,3 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

On May 19, 2021 Genmab A/S (Nasdaq: GMAB) reported that multiple abstracts evaluating several products in the company’s portfolio, or created using Genmab’s innovation, will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held virtually June 4-8, and at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress, being held virtually June 9-17 (Press release, Genmab, MAY 19, 2021, View Source [SID1234580275]). The presentations will include clinical data evaluating the investigational bispecific antibody epcoritamab (DuoBody-CD3xCD20) in patients with Non-Hodgkin Lymphoma (NHL), several studies evaluating Janssen Biotech, Inc. (Janssen)’s daratumumab and the subcutaneous formulation of daratumumab, and multiple abstracts evaluating Janssen’s bispecific program, which leverages Genmab’s DuoBody technology platform. In addition, trial-in-progress (TiPs) summaries of phase 3 trials evaluating epcoritamab and the investigational antibody-drug conjugate (ADC) tisotumab vedotin in patients with cervical cancer will be presented.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

All the abstracts have been published on the ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) websites and may be accessed online via the ASCO (Free ASCO Whitepaper) Meeting Library and the EHA (Free EHA Whitepaper) Open Access Library.

Epcoritamab is being co-developed by Genmab and AbbVie (NYSE: ABBV). Tisotumab vedotin is being co-developed by Genmab and Seagen Inc. (Nasdaq: SGEN), under an agreement in which the companies share all costs and profits for the product on a 50:50 basis. Daratumumab is being developed by Janssen under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab, and the companies have a collaboration to create and develop bispecific antibodies using Genmab’s DuoBody technology platform.

"The breadth and depth of the data being presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) demonstrate Genmab’s dedication to creating and developing a comprehensive portfolio of innovative and differentiated antibody medicines with the goal of improving the lives of people with cancer and their families," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We will continue to progress the investigational products in our pipeline, alone and together with our partners, to deliver new therapeutic options to patients in need."

Abstracts accepted for presentation at ASCO (Free ASCO Whitepaper) include:

Epcoritamab (DuoBody-CD3xCD20):

Subcutaneous Epcoritamab in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: Safety Profile and Anti-tumor Activity
Phase 3 Trial (GCT3013-05) of Epcoritamab Versus Standard of Care in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Tisotumab vedotin

Tisotumab Vedotin vs Investigator’s Choice Chemotherapy in Second- or Third-Line Recurrent or Metastatic Cervical Cancer (innovaTV 301/ENGOT‑cx12/GOG 3057, Trial in Progress)

Daratumumab:

Subcutaneous Daratumumab + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Patients With Newly Diagnosed Light Chain (AL) Amyloidosis: Updated Results From the Phase 3 ANDROMEDA Study
Daratumumab (DARA) Maintenance or Observation (OBS) After Treatment With Bortezomib, Thalidomide and Dexamethasone (VTd) With or Without DARA and Autologous Stem Cell Transplant (ASCT) in Patients (pts) With Newly Diagnosed Multiple Myeloma (NDMM): CASSIOPEIA Part 2
Abstracts accepted for presentation at EHA (Free EHA Whitepaper) include:

Epcoritamab (DuoBody-CD3xCD20):

Subcutaneous Epcoritamab in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: Safety Profile and Anti-tumor Activity

Daratumumab:

Subcutaneous Daratumumab + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Patients With Newly Diagnosed Light Chain (AL) Amyloidosis: Updated Results From the Phase 3 ANDROMEDA Study
Daratumumab (DARA) Maintenance or Observation (OBS) After Treatment With Bortezomib, Thalidomide and Dexamethasone (VTd) With or Without DARA and Autologous Stem Cell Transplant (ASCT) in Patients (pts) With Newly Diagnosed Multiple Myeloma (NDMM): CASSIOPEIA Part 2
Phase 3 Study of Daratumumab, Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Asian Patients with Newly Diagnosed Multiple Myeloma (NDMM): OCTANS

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to tumors to elicit an immune response towards malignant cells. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T cell mediated killing of lymphoma B cells.1 CD20 is a clinically validated therapeutic target, and is expressed on many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.2,3 Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.

About Tisotumab Vedotin
Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab’s fully human monoclonal antibody specific for tissue factor and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing target cell death. In cancer biology, tissue factor is a cell-surface protein and associated with tumor growth, angiogenesis, metastasis and poor prognosis.4 Based on its elevated expression in multiple solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach. Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

Tisotumab vedotin is being evaluated in a global phase 3, randomized clinical trial innovaTV 301, versus investigator’s choice of chemotherapy in recurrent or metastatic cervical cancer. The primary endpoint is overall survival and secondary endpoints include progression-free survival, duration of response, objective response rate, safety and tolerability. Enrollment is ongoing and the study is intended to support global registrations. In addition, tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in recurrent or metastatic cervical cancer, ovarian cancer, and other solid tumors and in combination with commonly used therapies in recurrent or metastatic cervical cancer. These trials are evaluating tisotumab vedotin on a weekly or every three-week dosing schedule. More information about the innovaTV 301 clinical trial, including enrolling sites, as well as other ongoing clinical trials is available at www.clinicaltrials.gov.

About DARZALEX(daratumumab)
DARZALEX (daratumumab) has become a backbone therapy in the treatment of multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with carfilzomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma who have received one to three previous lines of therapy; in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.5 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX is indicated for the treatment of adult patients in Europe via intravenous infusion or subcutaneous administration: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.6 Daratumumab is the first subcutaneous CD38 antibody approved in Europe for the treatment of multiple myeloma. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit www.DARZALEX.com.

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, is approved in the United States for the treatment of adult patients with newly diagnosed light-chain (AL) amyloidosis in combination with bortezomib, cyclophosphamide, and dexamethasone. It is also approved in the U.S. for the treatment of adult patients with multiple myeloma: in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for ASCT; in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for ASCT; in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy; in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and as monotherapy, in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology. DARZALEX FASPRO is the first subcutaneous CD38 antibody approved in the U.S. for the treatment of multiple myeloma and the first and only approved treatment for patients with AL amyloidosis in the U.S.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).5,8,9,10,11

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis and T-cell acute lymphocytic leukemia (ALL). Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.