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.

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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.

On May 19, 2021 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported updated interim clinical data, from the ongoing Phase 1/2 CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and Lymphoma) clinical trial, that will be presented in poster form at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting (Press release, Oncternal Therapeutics, MAY 19, 2021, View Source [SID1234580274]). In the CIRLL study, cirmtuzumab, an investigational anti-ROR1 monoclonal antibody, is being evaluated in combination with ibrutinib in patients with MCL and CLL. The clinical trial is being conducted in collaboration with UC San Diego School of Medicine and is partially funded by the California Institute for Regenerative Medicine.

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The updated interim data will be presented at the Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia session on June 7, 2021 as part of the ASCO (Free ASCO Whitepaper) 2021 Annual Meeting:

Abstract Title: Phase 1/2 Study of Cirmtuzumab and Ibrutinib in Mantle Cell Lymphoma (MCL) or Chronic
Lymphocytic Leukemia (CLL)
Abstract Number: 7556
Session Title: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Session Date and Time: June 7, 2021 at 11:30 am (Eastern Time)
"These updated clinical data with the combination of cirmtuzumab and ibrutinib remain very encouraging in heavily pre-treated patients with relapsed/refractory MCL, including the impressive 83% best ORR and the durability of complete responses. The enrolled patients also had negative prognostic features, making the results even more compelling. Deep responses to cirmtuzumab plus ibrutinib after prior ibrutinib therapy are particularly intriguing. We look forward to the continuing development of cirmtuzumab," said Hun Ju Lee, M.D., Associate Professor of Medicine in the Department of Lymphoma & Myeloma at the University of Texas MD Anderson Cancer Center, who is an investigator on the CIRLL clinical trial and the first author on the 2021 ASCO (Free ASCO Whitepaper) poster presentation.

"We are pleased that the interim results of the CIRLL study remain strong and consistent with further follow-up, including that median PFS and OS have still not been reached for these heavily pre-treated MCL and CLL patients. Adding cirmtuzumab to ibrutinib appears well tolerated, with no apparent additional toxicities noted to date," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "We are particularly pleased with our robust enrollment to date and the number and durability of CRs for the patients with MCL. We remain in active dialogue with the US FDA concerning potential pivotal study designs and the potential pathway to seeking regulatory approval."

The results that will be presented in poster form at ASCO (Free ASCO Whitepaper) 2021 include an increased population of 26 patients with relapsed/refractory MCL enrolled in the dose-finding and dose-expansion cohorts of the CIRLL clinical trial (Part 1 + Part 2), of whom 18 were evaluable for efficacy as of the April 16, 2021 data cut-off date.

Patients had high-risk factors and were heavily pre-treated at study entry, 70% with a high Ki-67 proliferative index (≥30%), 15% with intermediate/high sMIPI prognostic score, and a median of two systemic prior therapies (range 1-5).
The ORR of 83% (15 of 18 evaluable patients), which includes recently enrolled patients with relatively short follow-up time, is comparable to the 87% ORR (13 of 15 evaluable patients) previously presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting.
Eight of 18 (44%) evaluable patients achieved a partial response (PR) and two patients (11%) had stable disease (SD), for a total clinical best benefit rate (CR, PR, SD) of 94%.
The complete response rate was 39% (7 of 18 evaluable patients). CRs have remained durable, for 8-30+ months as of the data cutoff date.
The clinical benefit rate and median duration of response were favorable in patients with high-risk features associated with difficult to treat disease:
≥30% Ki-67: Clinical benefit rate of 89%; median duration of response of 14 months (95% CI: 8.66, NE)
>1 prior systemic therapy: Clinical benefit rate of 100%; median duration of response not reached
Four patients had received prior treatment with ibrutinib and all four achieved clinical responses, with two CRs and two PRs.
Median PFS and OS have not been reached, after a median follow-up of 18.9 months, regardless of number of prior systemic therapies, including three recently enrolled evaluable patients with a shorter follow-up time. Further, median PFS has not been reached for patients achieving a CR.
Historical data published for single agent ibrutinib for 370 patients with relapsed/refractory MCL from three clinical trials showed an ORR of 66%, CR rate of 20% and median PFS of 12.8 months (Rule et al., 2017, British Journal of Haematology).
As of the April 16, 2021 data cut-off date, 34 patients with CLL have been enrolled in the dose-finding and dose-confirming cohorts of this clinical trial (Part 1 & Part 2), of which 34 were evaluable for efficacy. The Company plans to present updated data from the randomized cohort (Part 3) in the second half of 2021.

Patients had high-risk factors, and most were heavily pre-treated at study entry, with 85% having RAI staging ≥2, 65% with lymphocytosis, and a median of two systemic prior therapies (range 1-15).
The ORR is similar, 94% (32 of 34 evaluable patients), compared to a 91% ORR presented for 31 of 34 evaluable patients at ASH (Free ASH Whitepaper) 2020.
The CR rate is 15% (5 of 34 evaluable patients), 3 CRs were unconfirmed. Twenty-seven patients (79%) achieved a PR and two patients (6%) had SD, for a total clinical benefit rate (CR, PR, SD) of 100%.
Median PFS and OS have not been reached, after a median follow up of 22.1 months, in this high risk and mostly heavily pre-treated CLL population.
The combination of cirmtuzumab plus ibrutinib has been well tolerated, with treatment emergent adverse events and hematologic abnormalities consistent with, or slightly lower than those reported for ibrutinib alone. There have been no dose-limiting toxicities and no serious adverse events attributed to cirmtuzumab alone.

About the CIRLL Clinical Trial
The CIRLL clinical trial (CIRM-0001) is a Phase 1/2 trial evaluating cirmtuzumab in combination with ibrutinib in separate groups of patients with CLL or MCL. Enrollment of the dose-finding cohorts in CLL and MCL, dose-expansion cohort in CLL and randomized Phase 2 cohort in CLL has been completed. Enrollment of the dose-expansion cohort in MCL is ongoing. Additional information about the CIRM-0001 clinical trial and other clinical trials of cirmtuzumab may be accessed at ClinicalTrials.gov.

About Cirmtuzumab
Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of MCL or CLL, in a collaboration with the University of California San Diego (UC San Diego) School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, Oncternal is supporting two investigator-sponsored studies being conducted at the UC San Diego School of Medicine: (i) a Phase 1b clinical trial of cirmtuzumab in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced, unresectable breast cancer, and (ii) a Phase 2 clinical trial of cirmtuzumab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory CLL.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen – not usually expressed on adult cells, and its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab, that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when cirmtuzumab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. The FDA has granted Orphan Drug Designations to cirmtuzumab for the treatment of MCL and CLL/small lymphocytic lymphoma. Cirmtuzumab is in clinical development and has not been approved by the FDA for any indication.

On May 19, 2021 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that sixteen abstracts have been selected for virtual presentation, including one oral presentation, at the upcoming 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 4-8, 2021 (Press release, Karyopharm, MAY 19, 2021, View Source [SID1234580273]).

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Key abstracts to be presented at the meeting will feature clinical data for XPOVIO (selinexor), the Company’s first in class, oral Selective Inhibitor of Nuclear Export (SINE) compound, including: (i) multiple new subgroup analyses from the pivotal Phase 3 BOSTON study, including data results evaluating XPOVIO treatment for patients over the age of 65 years old and patients with RAS-mutated multiple myeloma; (ii) updated data from the Pomalyst (pomalidomide) and Kyprolis (carfilzomib) arms of the Phase 1b/2 STOMP study evaluating XPOVIO in combination with backbone therapies in patients with relapsed or refractory multiple myeloma; (iii) new results from a Phase 1 study evaluating the combination of XPOVIO and pembrolizumab in advanced RAS mutant and RAS wild type colorectal cancer; (iv) results from gene set enrichment analyses identifying molecular predictors of response to XPOVIO from the Phase 2/3 SEAL study in patients with dedifferentiated liposarcoma (DDLS); and (v) updated overall survival (OS) data from a Phase 1/2 study evaluating oral eltanexor, the Company’s second generation SINE compound, in patients with hypomethylating-agent refractory myelodysplastic syndrome (MDS).

"We are honored to be sharing this broad set of clinical data with the medical and scientific community this year at ASCO (Free ASCO Whitepaper), where we will be highlighting several important new datasets, including new subgroup analyses from both the BOSTON and STOMP studies in patients with relapsed or refractory multiple myeloma where we believe XPOVIO will become an important backbone therapy," said Sharon Shacham, PhD, MBA, Chief Scientific Officer of Karyopharm. "Additionally, we are pleased to see data from our growing pipeline of solid tumor studies, which will include new data from an ongoing combination study of XPOVIO and pembrolizumab in patients with advanced colorectal cancer as well as the discovery of certain molecular predictors of response to XPOVIO in patients with dedifferentiated liposarcoma, a difficult to treat cancer due to its resistance to chemotherapy and radiation. The data presented this year continue to demonstrate the broad clinical utility of XPO1 inhibition across a growing range of cancer types."

Select Abstracts Featuring XPOVIO (selinexor) in Multiple Myeloma

1. Title: Survival Among Older Patients with Previously Treated Multiple Myeloma Treated with Selinexor, Bortezomib, and Dexamethasone (XVd) in the BOSTON study

Presenter: Thierry Facon, University Hospital
Abstract #: 8019
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: In an older patient population with a poor prognosis, XVd compared to Vd was associated with an OS benefit, improved progression-free survival (PFS) and an increased overall response rate (ORR) with reduced peripheral neuropathy and requires relatively short and infrequent clinic visits. XVd may be an effective regimen for patients 65 years of age or older. Adverse events (AEs) in this study were generally consistent with other previously reported selinexor studies in multiple myeloma.

2. Title: Effects of Weekly Selinexor, Bortezomib, Dexamethasone (XVd) Versus Standard Twice Weekly bortezomib and dexamethasone (Vd) on RAS-mutated previously treated multiple myeloma (MM)

Presenter: Christopher J. Walker, Karyopharm Therapeutics Inc.
Abstract #: 8027
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: Despite typically having the worst outcomes, patients with MM with any (K-, H- or N-) RAS mutation had a similar benefit from XVd as RAS wild-type MM, showing that the XVd combination can overcome therapy resistance characteristic of RAS-mutated MM. Mechanistically, selinexor induced down regulation of germinal center kinase and enhanced killing of RAS-mutated MM cells. With a manageable safety profile, the XVd regimen was able to overcome the therapeutic resistance of RAS-mutated multiple myeloma and improved PFS and OS in patients with RAS-mutated MM, and the data suggest that selinexor-containing regimens could be active in other RAS-mutant cancers. AEs in this study were generally consistent with other previously reported selinexor studies in MM.

3. Title: Effects of Refractory Status to Lenalidomide on Safety and Efficacy of Selinexor, Bortezomib, and Dexamethasone (XVd) Versus Bortezomib and Dexamethasone (Vd) in Patients with Previously Treated Multiple Myeloma

Presenter: Xavier Leleu, CHU de Poitiers, Hôpital La Mileterie
Abstract #: 8024
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: In patients with previously treated multiple myeloma, PFS, ORR, and time to next treatment were significantly improved regardless of documented refractory status to any immunomodulatory drug (IMiD) or to lenalidomide specifically. These analyses support the use of the XVd combination for patients with disease refractory to lenalidomide and likely to any IMiD. AEs in this study were generally consistent with other previously reported selinexor studies in multiple myeloma.

4. Title: Oral Selinexor, Pomalidomide, and Dexamethasone (XPd) at Recommended Phase 2 Dose in Relapsed Refractory Multiple Myeloma (MM)

Presenter: Darrell White, QEII Health Sciences Center, Dalhousie University
Abstract #: 8018
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster Discussion Presentation
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: Once-weekly selinexor was shown in this Phase 1b/2 study to be safely combined with Pomalyst (pomalidomide) and low-dose dexamethasone (XPd) in patients with heavily pretreated MM. This all-oral XPd combination is highly active with an ORR of 65% at the recommended Phase 2 dose in 20 patients, compared to the expected ORR of ≤30% for the combination of Pomalyst and dexamethasone (Pd) or selinexor and dexamethasone, and has thus far produced durable responses with a median PFS of 12.2 months. The data suggest that the regimen was active even in patients with daratumumab-refractory MM. AEs in this study were generally consistent with other previously reported selinexor studies in multiple myeloma.

5. Title: Once Weekly Selinexor, Carfilzomib, and Dexamethasone (XKd) in Carfilzomib Nonrefractory Multiple Myeloma (MM) Patients

Presenter: Cristina Gasparetto, Duke University Cancer Center
Abstract #: 8038
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: In 27 patients with heavily pretreated MM (median of 4 lines of prior therapy), weekly XKd is highly active with an ORR of 78% and deep responses (≥VGPR 41%) with an overall PFS of 15 months; activity was strong even in patients with daratumumab refractory disease. AEs in this Phase 1/2b study were generally consistent with other previously reported selinexor studies in MM.

6. Title: Selinexor Containing Regimens in Patients with Multiple Myeloma (MM) Previously Treated with anti-CD38 Monoclonal Antibodies (aCD38 mAbs)

Presenter: Cristina Gasparetto, Duke University Cancer Center
Abstract #: e20020
Session type: Online abstract
Highlights: Selinexor-containing triplet combinations in 47 patients with MM previously treated with anti-CD38 mAb, most of whom had triple-class refractory MM, exhibit tolerability and comparable effectiveness to their most recent anti-CD38 mAb-containing regimens in this retrospective analysis. Compared to historical controls who did not receive selinexor, median OS was much longer among these patients. The results show that selinexor-containing regimens maintain high levels of anti-MM activity, even in patients whose disease is refractory to daratumumab, immunomodulatory drugs and proteasome inhibitors. AEs in this study were generally consistent with other previously reported selinexor studies in multiple myeloma.

Select Abstracts Featuring XPOVIO (selinexor) in Solid Tumors

7. Title: Molecular Predictors of Response to Selinexor in Advanced Unresectable De-differentiated Liposarcoma (DDLS)

Presenter: Christopher J. Walker, Karyopharm Therapeutics Inc.
Abstract #: 11509
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Oral presentation
Session: Emerging Trends in Sarcoma Precision Medicine
Highlights: The randomized Phase 3 SEAL study of selinexor versus placebo in patients with heavily pretreated DDLS showed a significant improvement in PFS for selinexor. The molecular analyses reported here demonstrate that DDLS tumors responding to selinexor showed low expression of CALB1 and high GRM1. If validated, patients with DDLS whose tumors match this expression profile are especially likely to benefit from selinexor.

8. Title: Open-Label Phase 1 Study Evaluating the Tolerability and Anti-Tumor Activity of Selinexor and Pembrolizumab in Colorectal Cancer

Presenter: Talia Golan, Oncology Department Center Sheba Medical Center at Tel Hashomer
Session type: Online abstract
Abstract #: e15579
Highlights: Selinexor in combination with pembrolizumab has demonstrated disease control in patients with chemotherapy refractory, advanced/metastatic, microsatellite stable colorectal cancer (CRC). Greater anti-tumor activity was observed in patients with RAS mutations despite the absence of high microsatellite instability and/or deficient in mismatch repair. The therapy was well tolerated with no unanticipated adverse events observed.

9. Title: Selinexor in Combination with Weekly Paclitaxel in Patients with Advanced or Metastatic Solid Tumors: Results of an Open Label, Single-Center, Multi-arm Phase 1b Study

Presenter: Shannon Westin, The University of Texas MD Anderson Cancer Center
Abstract #: 5565
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Gynecologic Cancer
Highlights: Among 24 evaluable patients with heavily pretreated ovarian cancer, oral selinexor in combination with weekly paclitaxel resulted in an ORR of 17% and a clinical benefit rate (response + stable disease >12 weeks) of 58%. With prior taxane therapy, the ORR was 10% and with no prior taxane therapy, the ORR was 23%. The combination demonstrated promising clinical activity with manageable toxicity.

Abstracts Featuring Eltanexor in MDS

10. Title: Updated Overall Survival of Eltanexor for the Treatment of Patients with Hypomethylating Agent Refractory Myelodysplastic Syndrome

Presenter: Sangmin Lee, Weill Cornell Medical College
Abstract #: e19037
Session type: Online abstract
Highlights: Single-agent oral eltanexor was active in patients with high-risk, hypomethylating agent refractory MDS. Of the 20 enrolled patients, seven (35%) had marrow complete response (mCR), and five (25%) had stable disease (SD) for a total disease control (mCR+SD) rate of 60%. Of the 15 patients evaluable for efficacy, seven (47%) had mCR and five (33%) had SD. Patients who reached mCR (n=7) had significantly longer median OS than patients without mCR (n=8) or with progressive disease (n=3). Side effects were consistent with other studies of eltanexor without solid organ toxicity. Further evaluation of eltanexor in MDS as a single agent and in combination with other agents is ongoing.

Additional Abstracts to be Presented

11. Title: A Randomized, Open-label, Phase 3 Study of Low-dose Selinexor and Lenalidomide (Len) Versus Len Maintenance Post Autologous Stem Cell Transplant (ASCT) for Newly Diagnosed Multiple Myeloma (NDMM): ALLG MM23: Sealand

Presenter: Hang Quach, St. Vincent Hospital
Abstract #: TPS8055
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia

12. Title: U.S. Budget Impact (BI) Model for Selinexor, Bortezomib, and Dexamethasone (XVd) for the Treatment of Patients with Previously Treated Multiple Myeloma (MM)

Presenter: Mike Dolph, McGill University
Abstract #: e18839
Session type: Online abstract

13. Title: SIENDO/ENGOT-EN5/GOG-3055: A Randomized Phase 3 Trial of Maintenance Selinexor Versus Placebo After Combination Platinum-based Chemotherapy in Advanced or Recurrent Endometrial Cancer

Presenter: Ignace Vergote, BGOG and University Hospitals Leuven, Leuven Cancer Institute
Abstract #: TPS5610
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Gynecologic Cancer

14. Title: A Phase 1/2 Study of Selinexor in Combination with Standard of Care Therapy for Newly Diagnosed or Recurrent Glioblastoma

Presenter: Yazmin Odia, Miami Cancer Institute, Baptist Health South Florida (BHSF)
Abstract #: TPS2071
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Central Nervous System Tumors

15. Title: Digital Measurement of Functional Status of Patients with Glioblastoma

Presenter: Yasaman Demastani, Karyopharm Therapeutics Inc.
Abstract #: 2016
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Central Nervous System Tumors

16. Title: A Phase 1b/2 Study of Selinexor in Combination with Imatinib in Patients with Advanced Gastrointestinal
Stromal Tumor (GIST): SeliGIST/GEIS-41 Trial

Presenter: Cesar Serrano, West Virginia University School of Medicine Neurology & Neurosurgery
Abstract #: 11534
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Sarcoma

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. NEXPOVIO (selinexor) has also been granted conditional marketing authorization for adult patients with heavily pretreated multiple myeloma by the European Commission. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection(21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1–888–209–9326 or FDA at 1–800–FDA–1088 or www.fda.gov/medwatch.

About Eltanexor (KPT-8602)

Eltanexor (KPT-8602) is a second generation oral SINE compound, which is currently being investigated in clinical trials. Eltanexor functions by binding to and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. Eltanexor has demonstrated minimal brain penetration in animals, which has been associated with reduced toxicities in preclinical studies while maintaining potent anti-tumor effects.

On May 19, 2021 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products reported updated data from the Company’s ongoing Phase 1/2 study evaluating ADXS-503 in combination with KEYTRUDA which will be presented as a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting (Press release, Advaxis, MAY 19, 2021, View Source [SID1234580272]). ADXS-503 is the first drug construct from the ADXS-HOT off-the-shelf, cancer-type specific, immunotherapy program which leverages Advaxis’ proprietary Lm technology platform to target hotspot mutations that commonly occur in specific cancer types as well as other proprietary, tumor-associated antigens.

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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

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"These early results, which include a disease control rate of 44% in the first 9 evaluable patients treated with ADXS-503 as an add on therapy at progression with pembrolizumab, are particularly encouraging given the durable nature of disease control in 3 patients," said Suresh Ramalingam, M.D., Roberto C. Goizueta Chair for Cancer Research, Director, Division of Medical Oncology and Deputy Director of the Winship Cancer Institute at Emory University School of Medicine. "The translational results from the study provide interesting insights on the potential mechanism of action by which the addition of ADXS-503 may may be effective in this patient population."

Ken Berlin, Chief Executive Officer of Advaxis, said, "We are encouraged by these updated results which continue to support the potential of ADXS-503 to enhance and/or restore sensitivity to checkpoint inhibitors. The clinical activity observed to date in this challenging patient population, combined with a favorable safety profile, suggest that ADXS-503 may be an important new off-the-shelf immunotherapy treatment option. We look forward to continued progress in the clinic with our ADXS-HOT products which includes the ongoing Phase 1/2 study of ADXS-503 in NSCLC, and the expansion of the program to our planned Phase 1 Study of ADXS-504 for the treatment of early prostate cancer."

Key presentation highlights:

Highlights from the poster presentation titled, "A phase 1 study of an off-the-shelf, multi-neoantigen vector (ADXS-503) in patients with metastatic non-small-cell lung cancer (NSCLC) progressing on pembrolizumab as last therapy" presented by Missak Haigentz, M.D., Section Chief of Hematology and Oncology at Morristown Medical Center and Medical Director of Hematology and Oncology for Atlantic Health, and Study Investigator, include:

10 patients have been treated with ADXS-503 as an add on therapy to patients failing pembrolizumab as last therapy with 10 patients evaluable for safety and 9 patients evaluable for efficacy

Combination therapy was well tolerated with no DLTS or added toxicity of the two drugs. Grade 1 and 2, transient and reversible events included chills, fever, fatigue, in approximately half of the patients

The Disease Control Rate (DCR) was 44% (4/9)

Clinical benefit was durable, with an observed partial response (PR) and stable disease (SD) sustained for over a year, and another observed SD lasting over 6 months. An additional PR was maintained for approximately 4 months

Biomarker data demonstrate that patients who seem to achieve clinical benefit include those with PD-L1 expression ≥50%, secondary resistance disease to pembrolizumab and those who show proliferation and/or activation of NK and CD8+ T cells within the first weeks of therapy

Translational studies show:

Antitumoral T-cell responses elicited against hot-spot mutation antigens and/or tumor associated antigens (TAAs)

Emergence of naive CD8+ Tcell clones, suggesting reactivity against novel antigens

Induction of proliferation and/or activation of pre-existing CD8+ T-cell clones, including PD-1 upregulation

Enrollment in Part B of the ongoing study will continue to further evaluate the clinical benefit and immune effects of adding on ADXS-503 to patients progressing on pembrolizumab
The Phase 1/2 clinical trial of ADXS-503 is seeking to establish the recommended dose, safety, tolerability and clinical activity of ADXS-503 administered alone and in combination with a KEYTRUDA in approximately 50 patients with NSCLC, in at least five sites across the U.S. The two dose levels with monotherapy in Part A, (1 X108 and 5 X108 CFU) have been completed. Part B with ADXS-503 (1 X108 CFU) in combination with KEYTRUDA is currently enrolling its efficacy expansion for up to 18 patients at dose level 1 (1 X108 CFU + KEYTRUDA) with the potential to proceed to dose level 2 (5 X108 CFU + KEYTRUDA) at a later date. Part C, which is evaluating ADXS-503 in combination with KEYTRUDA (1 X108 CFU + KEYTRUDA) as a first line treatment for patients with NSCLC with PD-L1 expression ≥ 1% or who are unfit for chemotherapy is currently enrolling patients.

About ADXS-HOT
ADXS-HOT is a program that leverages the Company’s proprietary Lm technology to target hotspot mutations that commonly occur in specific cancer types. ADXS-HOT drug candidates are designed to target acquired shared or "public" mutations in tumor driver genes along with other proprietary cancer-testes and oncofetal tumor-associated antigens that also commonly occur in specific cancer types. ADXS-HOT drug candidates are an off-the-shelf treatment, designed to potentially treat all patients with a specific cancer type, without the need for pretreatment biomarker testing, DNA sequencing or diagnostic testing.

On May 19, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, reported results from a randomized confirmatory Phase 2 study of ficlatuzumab as a single agent or in combination with cetuximab (ERBITUX), an EGFR-targeted antibody, in patients who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab (pan-refractory) with metastatic head and neck squamous cell carcinoma (HNSCC) (Press release, AVEO, MAY 19, 2021, View Source [SID1234580271]). Ficlatuzumab is AVEO’s potent humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets hepatocyte growth factor (HGF). The results will be presented by lead investigator Julie E. Bauman, M.D., MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Deputy Director, University of Arizona Cancer Center, at a poster discussion session of the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held June 4-8 in a virtual setting.

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"Human papillomavirus (HPV) negative HNSCC is associated with poorer outcomes compared to HPV positive disease, particularly in pan-refractory disease, where there are currently no effective treatment options," said Professor Bauman. "Crosstalk between EGFR and HGF/cMet pathways is a known tumor intrinsic resistance mechanism, and HGF expression is known to be high in HPV negative disease, suggesting that the simultaneous inhibition of these pathways with cetuximab and ficlatuzumab could enhance anti-cancer response in this population. Results from this study are highly encouraging, with notable activity in pan-refractory, HPV negative disease warranting Phase 3 investigation."

"Results in patients with HPV negative disease who received ficlatuzumab and cetuximab produced prolonged progression free survival (PFS) and a response rate of 38%, which included two (18%) complete responses (CRs). These results suggest the combination has the potential to play a meaningful role in the treatment and the ultimate quality of life of patients with relapsed/metastatic HNSCC," said Michael Bailey, president and chief executive officer of AVEO. "The results compare favorably to historical controls of cetuximab in earlier lines of treatment. After receiving FDA feedback, we look forward to making a go/no-go decision by mid-year on the initiation of a Phase 3 study in an HPV negative HNSCC patient population, which we would expect to initiate in the first half of 2022, upon the availability of clinical drug supply."

In the Phase 2 study, a total of 60 patients with metastatic HNSCC who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab were randomized 1:1 to receive either ficlatuzumab alone (20 mg/kg IV) or ficlatuzumab in combination with cetuximab (500 mg/m2 IV) every two weeks. The ficlatuzumab/cetuximab combination arm met the study’s primary endpoint of median PFS, with the 32 evaluable patients in the arm demonstrating a median PFS of 3.6 months (lower bound 90% confidence interval [CI] 2.3 months; p=0.04), and 1.8 months (lower bound 90% CI: 1.7 months) for the 26 evaluable patients receiving ficlatuzumab alone. For the key secondary endpoint of overall response rate (ORR), the combination arm demonstrated an ORR of 19%, and 4% for ficlatuzumab alone.

Enrolled patients were stratified by HPV status, as HPV negative patients are known to have poorer outcomes. In an exploratory comparison of the HPV positive (n=16) and HPV negative (n=16) subgroups of the combination arm, HPV negative patients demonstrated both a superior ORR of 38% (versus 0% for HPV positive, p=0.02), with two CRs and four partial responses, and a median PFS of 4.1 months (versus 2.3 months for HPV positive, p=0.03). These results reflect updated data from those available at the time of abstract submission.

The combination of ficlatuzumab and cetuximab was generally well-tolerated with expected class toxicities from HGF/cMet inhibitors observed, including common adverse events of edema and hypoalbuminemia, and an uncommon adverse event of pneumonitis. Two treatment related deaths occurred, including pneumonitis (ficlatuzumab arm) and cardiopulmonary arrest (combination arm).

A copy of the poster will be available at www.aveooncology.com after its presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

ASCO Presentation Details

Title: Randomized Phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, advanced head and neck squamous cell carcinoma (HNSCC).
Presenter: Julie E. Bauman, M.D., MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Associate Director of Translational Research, University of Arizona Cancer Center
Abstract: 6015
Track: Head and Neck Cancer
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
About Ficlatuzumab

Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) immunoglobulin G1 (IgG1) inhibitory antibody that binds to the HGF ligand with high affinity and specificity. HGF is the natural ligand of c-Met and blocking HGF inhibits signaling through the HGF/c-Met signaling pathway. Ficlatuzumab is currently being evaluated in squamous cell carcinoma of the head and neck (HNSCC) and metastatic pancreatic ductal cancer (PDAC).