On May 26, 2022 NKGen Biotech Inc., a biotechnology company harnessing the power of the body’s immune system through the development of Natural Killer (NK) cell therapies, reported that clinical data from its ongoing SNK01 (NK cell therapy) phase I trial, in patients with advanced solid tumors, will be presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 3 – 7, 2022 in Chicago, Illinois (Press release, NKGEN Biotech, MAY 26, 2022, View Source [SID1234615095]).

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!

Results will be presented in a poster discussion entitled: Interim analysis of a phase I study of SNK01 (autologous non-genetically modified natural killer cells with enhanced cytotoxicity) and avelumab in advanced refractory sarcoma (abstract: 11517; poster: 422), on Sunday, June 5, 2022, 8:00 am – 11:00 am; Discussion 11:30 am – 1:00 pm CDT; Sarcoma session, sarcoma track, Room S404.
The SNK01 phase I, open label, dose escalation trial (NCT03941262), in patients with advanced solid tumors refractory to conventional treatment, demonstrated antitumor activity and an acceptable safety profile.

Key highlights

SNK01 combined with avelumab showed efficacy in 17 advanced stage cancer patients (all heavily pre-treated with a median of 5 lines of prior therapy)
Best ORR is 11.7% with 2 PR and 7 SD
Median PFS is 11.3 weeks; four patients (23.5%) have PFS of > 41 weeks
Median OS is 24.9 weeks
PFS and OS are expected to increase as patients continue on the trial
SNK01 combined with avelumab was safe and well-tolerated and appears to have some clinical activity against several types of heavily pre-treated advanced sarcomas, independent of PD-L1 status
SNK01 may also keep rapidly progressing disease stable while allowing additional treatment with cytotoxic chemotherapy
Two additional posters will also be presented at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting:

Preliminary analysis of a phase I study of SNK01 (Autologous non-genetically modified natural killer cells with enhanced cytotoxicity) monotherapy in patients with advanced solid tumors (abstract: 2644, poster: 298)
The combination of CD16A/EGFR innate cell engager, AFM24, with SNK01 autologous natural killer cells in patients with advanced solid tumors (abstract: TPS2675, poster: 326b)
Abstracts presented at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting can be found at www.asco.org

On 26, 2022 Incyte (Nasdaq:INCY) reported that multiple abstracts featuring data from its oncology portfolio will be presented at the upcoming European Hematology Association (EHA) (Free EHA Whitepaper) 2022 (EHA2022) Congress (June 9-17; virtual and in Vienna) (Press release, Incyte, MAY 26, 2022, View Source [SID1234615111]).

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!

"We are committed to advancing science that can lead to solutions for patients with serious unmet medical needs, including those with cancer"

"We are committed to advancing science that can lead to solutions for patients with serious unmet medical needs, including those with cancer," said Steven Stein, M.D., Chief Medical Officer, Incyte. "For that reason, we look forward to convening with the oncology community and presenting data from across our portfolio, including both Incyte-led and partnered programs."

Key abstracts accepted by EHA (Free EHA Whitepaper) include:

Oral Presentation

Long-term Efficacy and Safety Results from an Ongoing Open-Label Phase 2 Study of Parsaclisib for the Treatment of Autoimmune Hemolytic Anemia (AIHA) (Abstract #S286. Session: Transfusion and Autoimmune Hemolytic Anemia. Session Time: Friday, June 10, 11:30 a.m. – 12:45 p.m.)

Poster Presentations

A Real-World Evaluation of the Association Between Elevated Blood Counts and Thrombotic Events in Polycythemia Vera: An Analysis of Data from the Reveal Study (Abstract #P1062. Session: Myeloproliferative neoplasms – Clinical)

Does Early Intervention in Myelofibrosis Impact Outcomes? A Pooled Analysis of the COMFORT 1 and 2 Studies (Abstract #P1037. Session: Myeloproliferative neoplasms – Clinical)

Ruxolitinib Demonstrates a Greater Corticosteroid-Sparing Effect than Best Available Therapy in Patients with Corticosteroid-Refractory/Dependent Chronic Graft-Vs-Host Disease1 (Abstract #P1389. Session: Stem cell transplantation – Clinical)

Real-World Safety of Ruxolitinib in Patients with Intermediate or High Risk of Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis in China1 (Abstract #P1047. Session: Myeloproliferative neoplasms – Clinical)

Efficacy and Safety of Parsaclisib-Ruxolitinib Combination Therapy in Myelofibrosis Patients with Low vs Higher Baseline Platelet Count: A Subgroup Analysis of Data from a Phase 2 Study (Abstract #P1063. Session: Myeloproliferative neoplasms – Clinical)

A Phase 1 Study Evaluating Safety and Efficacy of Parsaclisib in Combination with Bendamustine + Obinutuzumab in Patients with Relapsed or Refractory Follicular Lymphoma (CITADEL-102) (Abstract #P1104. Session: Indolent and mantle-cell non-Hodgkin lymphoma – Clinical)

A Phase 1 Study of Parsaclisib in Combination with Investigator Choice of Rituximab, Bendamustine + Rituximab, or Ibrutinib in Patients with Previously Treated B-Cell Lymphoma (CITADEL-112): Preliminary Safety Results (Abstract #P1102. Session: Indolent and mantle-cell non-Hodgkin lymphoma – Clinical)

inMIND: A Phase 3 Study of Tafasitamab Plus Lenalidomide and Rituximab Versus Placebo Plus Lenalidomide and Rituximab for Relapsed/Refractory Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) (Abstract #P1103. Session: Indolent and mantle-cell non-Hodgkin lymphoma – Clinical)

Real-Life Effectiveness and Safety Outcomes of Ponatinib Treatment in Patients with Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (PH+ALL): 5-Year-Data from a Belgian Registry (Abstract #P699. Session: Chronic myeloid leukemia – Clinical)

Dose Modification Dynamics of Ponatinib in Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) from the PACE and OPTIC Trials2 (Abstract #P707. Session: Chronic myeloid leukemia – Clinical)

All (e)Poster presentations will be made available as of Friday, June 10, 2022, at 3:00 a.m. EST and will be accessible for on-demand viewing until Monday, August 15, 2022, on the Congress platform. For full session details and data presentation listings, please see the EHA (Free EHA Whitepaper)2022 online program (View Source).

About Ruxolitinib (Jakafi)
Ruxolitinib (Jakafi) is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. FDA for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea, in adults with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF, for treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older and for the treatment of chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

Jakafi is marketed by Incyte in the U.S. and by Novartis as Jakavi (ruxolitinib) outside the U.S. Jakafi is a registered trademark of Incyte. Jakavi is a registered trademark of Novartis AG in countries outside the U.S.

About Tafasitamab (Monjuvi / Minjuvi)
Tafasitamab is a humanized Fc-modified CD19 targeting immunotherapy. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb 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).

In the United States, Monjuvi (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 DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for ASCT. This indication is approved under accelerated approval based on overall response rate. Full approval for this indication may be contingent upon results in a confirmatory trial(s).

In Europe, Minjuvi (tafasitamab) received conditional approval, in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

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

Minjuvi and Monjuvi are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi in the U.S. and marketed by Incyte under the brand name Minjuvi in the EU.

XmAb is a registered trademark of Xencor, Inc.

About Ponatinib (Iclusig) Tablets
Ponatinib (Iclusig) targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.

In the EU, Iclusig is approved for the treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, or the treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.

Click here to view the Iclusig EU Summary of Medicinal Product Characteristics.

Incyte has an exclusive license from Takeda Pharmaceuticals International AG to commercialize ponatinib in the European Union and 29 other countries, including Switzerland, UK, Norway, Turkey, Israel and Russia. Iclusig is marketed in the U.S. by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

About Parsaclisib
Parsaclisib is a potent, highly selective, next-generation investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ). It is currently under evaluation as a monotherapy in non-Hodgkin lymphomas and autoimmune hemolytic anemia, and in combination with ruxolitinib and tafasitamab for myelofibrosis and non-Hodgkin lymphomas, respectively.

In December 2018, Innovent and Incyte entered into a strategic collaboration for three clinical-stage product candidates, including parsaclisib. Under the terms of the agreement, Innovent has received the rights to develop and commercialize parsaclisib and two other assets in Mainland China, Hong Kong, Macau and Taiwan.

On May 26, 2022 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing next-generation multifunctional biotherapeutics, reported new clinical data for the HER2‑targeted bispecific antibody zanidatamab in both HER2-positive breast cancer and gastric/gastroesophageal junction adenocarcinoma (Press release, Zymeworks, MAY 26, 2022, View Source [SID1234615127]). The data are being presented in two separate poster sessions at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting June 3-7, 2022 in Chicago, IL.

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!

"These encouraging new data sets presented at ASCO (Free ASCO Whitepaper) provide further validation of zanidatamab’s potential in the treatment of advanced HER2-positive cancers and follow the release of other promising data in gastroesophageal and breast cancer in 2021," said Neil Josephson, M.D., Chief Medical Officer at Zymeworks. "These new data continue to demonstrate the potential for zanidatamab to be an important advancement in the treatment of a wide range of HER2-expressing cancers, including in first-line treatment regimens."

The presentations detailed below are available to conference registrants on the ASCO (Free ASCO Whitepaper) conference website as well as to the general public at www.zymeworks.com/publications.

Poster Session: Zanidatamab in Combination with Chemotherapy and Tislelizumab in HER2-Positive Gastric/Gastroesophageal Junction Cancer – Clinical Results – Saturday, June 4, 08:00-11:00 am CDT

Zanidatamab, a HER2-targeted bispecific antibody, in combination with chemotherapy and tislelizumab as first-line therapy for patients with advanced HER2-positive gastric/gastroesophageal junction adenocarcinoma (G/GJEC): Preliminary results from a Phase 1b/2 study

Presenter: Keun Wook Lee, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

Over one million patients are diagnosed with gastric cancer every year worldwide, and it is the fourth most common cause of cancer-related deaths1. Human epidermal growth factor receptor 2 (HER2)-positive disease accounts for 15–25% of gastric cancers2. For these patients, trastuzumab in combination with chemotherapy is the global standard of care treatment but with an expected overall survival of less than 18 months, there remains a significant unmet need.

In 33 response-evaluable patients with advanced HER2-positive gastric/gastroesophageal junction adenocarcinoma treated with zanidatamab and tislelizumab in combination with the CAPOX chemotherapy regimen the cORR was 75.8% (25/33). The DCR was 100% (33/33) and duration of response (DOR) ranged from 2.1+ to 18.2+ months. Twenty patients (61%) remain on study at the time of data cut-off.

In addition, the data demonstrate that zanidatamab and tislelizumab in combination with the CAPOX chemotherapy is generally well tolerated, with the majority of treatment-related adverse events (TRAEs) considered mild to moderate in severity (Grade 1 or 2). The most common grade ≥ 3 TRAE was diarrhea, which was manageable in the outpatient setting; introduction of prophylactic loperamide reduced the incidence from 33% to 21%. Immune mediated adverse events occurred in 27% of patients, including ≥ Grade 3 events in 21% of patients and resulted in discontinuation of tislelizumab in 3 patients (9%). This manageable safety profile compares favorably to the current standard of care as well as to emerging treatments and is consistent with previous reports.3

This new data set further supports the launch of Zymeworks’ global Phase 3 study (HERIZON-GEA-01; NCT05152147), which is investigating zanidatamab in combination with chemotherapy with or without tislelizumab for first-line treatment of locally advanced, unresectable, or metastatic HER2-positive gastroesophageal adenocarcinoma. Zymeworks, along with its Asia-Pacific partner BeiGene, plan to enroll 714 patients at approximately 300 sites across 38 countries. Enrollment is expected to be completed by the end of 2023. The study design will be presented in a Trials in Progress poster (Poster ID: P-26) at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer taking place in Barcelona, Spain from June 29-July 2, 2022. The presentation will be available to conference registrants on the conference website as well as to the general public at www.zymeworks.com/publications at the time of presentation at the conference.

Poster Session: Zanidatamab in Combination with Docetaxel in HER2-Positive Breast Cancer – Clinical Results – Monday, June 6, 08:00-11:00 am CDT

Zanidatamab, a HER2-targeted bispecific antibody, in combination with docetaxel as first-line therapy for patients with advanced HER2-positive breast cancer: Preliminary results from a Phase 1b/2 study

Presenter: Keun Seok Lee, National Cancer Center, Center for Breast Cancer, Goyang, Republic of Korea

Worldwide, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths in women, with over 650,000 deaths in 20201,4. HER2-positive breast cancer accounts for approximately 20% of all breast cancers5,6,7. Though HER2-targeted agents have improved outcomes in HER2-positive breast cancer, most patients treated for advanced disease eventually relapse and develop resistant disease8,9.

In 21 response-evaluable patients with advanced HER2-positive breast cancer treated with zanidatamab and docetaxel the cORR was 90.5%, with 15 patients (78.9%) having an ongoing response at the time of the data cut. The median follow-up was 7.0 months (range 1.1-17.4 months) and the six-month progression-free survival rate was 95.2%.

The combination of zanidatamab and docetaxel had a manageable safety profile with the incidence of TRAEs consistent with standard of care therapy. The most common TRAEs were neutrophil count decreased (13 patients; 54.2%), diarrhea (13 patients; 54.2%), and anemia (nine patients; 37.5%), and the most common ≥ Grade 3 TRAEs were neutrophil count decreased (12 patients; 50.0%), diarrhea (3 patients; 12.5%), and white blood cell count decreased (2 patients; 8.3%).

"We will continue to support ongoing R&D efforts to generate and report robust data highlighting and reinforcing the potential applications of our therapeutics and technology platforms in the treatment of a wide range of diseases," said Kenneth Galbraith, Chair and CEO of Zymeworks. "We remain focused on exploring potential research and collaboration opportunities that can lead to a broader portfolio of innovative therapies for patients in need around the world with difficult-to-treat cancers."

Conference Call and Webcast

Zymeworks will host a conference call and webcast on Monday, June 6th at 4:30 pm ET to discuss the clinical data presented at ASCO (Free ASCO Whitepaper) and provide an overview on the clinical development strategy for zanidatamab. The event will be led by Kenneth Galbraith, Zymeworks’ Chair and CEO, and Neil Josephson, M.D., Zymeworks’ Chief Medical Officer. Members of Zymeworks’ executive team will be available to answer questions at the conclusion of the call.

Interested parties can access the live webcast via the Zymeworks’ website at View Source A recorded replay will be accessible after the event through the Zymeworks website.

About Zanidatamab

Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding, and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2, and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. The FDA has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified biliary tract cancer (BTC), and two Fast Track designations to zanidatamab, one as a single agent for refractory BTC and one in combination with standard of care chemotherapy, for first-line gastroesophageal adenocarcinoma (GEA). These designations mean zanidatamab is eligible for Accelerated Approval, Priority Review and Rolling Review, as well as intensive FDA guidance on an efficient drug development program. Zanidatamab has also received Orphan Drug designations for the treatment of biliary tract, gastric and ovarian cancers, as well as Orphan Drug designation for the treatment of gastric cancer from the European Medicines Agency.

On May 26, 2022 Gracell Biotechnologies Inc. ("Gracell" or the "Company",NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported that it will present updated clinical data from a multicenter investigator-initiated trial (IIT) evaluating GC012F, the company’s B-cell maturation antigen (BCMA) and CD19 dual-targeting CAR-T candidate, for the treatment of relapsed/refractory multiple myeloma (RRMM) in an oral abstract presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO 2022) Annual Meeting (Press release, Gracell Biotechnologies, MAY 26, 2022, View Source [SID1234615143]).

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!

GC012F is an autologous CAR-T therapeutic candidate dual-targeting BCMA and CD19, developed using Gracell’s proprietary FasTCAR platform, which enables next-day manufacturing of CAR-T therapies. In November 2021, GC012F was granted Orphan Drug Designation for the treatment of multiple myeloma (MM) by the U.S. Food and Drug Administration. GC012F is currently being evaluated in IITs in China including in MM and B-NHL.

"We are thrilled to present updated data from our ongoing study of GC012F for the treatment of patients with RRMM at the oral abstract session at ASCO (Free ASCO Whitepaper)," said Dr. Martina A. Sersch, Chief Medical Officer of Gracell. "GC012F is the first dual-targeting CAR-T with clinical data in RRMM, which is designed to improve depth of response as well as tackling some of the major challenges of CAR-T therapy, including the need for faster delivery to the patients in need . We have followed patients for over two and a half years and also enrolled new patients into the study. RRMM still remains an area of unmet medical need, including the need of deepening responses for eligible patients."

From October 2019 to November 2021, 28 heavily pretreated RRMM patients were enrolled and treated in this single-arm, open label, multicenter IIT with a single infusion of GC012F at three dose levels: 1×105 cells/kg (DL1), 2×105 cells/kg (DL2), and 3×105 cells/kg (DL3). An additional 9 patients were treated in three different dose levels since the last update reported at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) in 2021. 89.3% (25/28) patients were high risk based on mSMART 3.0 criteria and patients had received a median of five prior lines of therapy.

At the data cutoff of January 26, 2022, the 28 patients had been evaluated for response with a median follow-up time of 6.3 months, ranging from 1.8 to 29.9 months. Patients are continued to be followed for deepening responses. The response rate at different dose levels was 100% (2/2) in DL1, 80% (8/10) in DL2, and 93.8% (15/16) in DL3. All (27/27, 100%) MRD-assessable patients achieved minimal residual disease (MRD) negativity. 75% (21/28) of all patients treated achieved MRD- sCR.

The safety profile of GC012F was consistent with previous findings with mostly low grade of cytokine release syndrome (CRS) (Grade 0-2 (93%)). No Grade 4 or 5 CRS, or any Grade immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. Patients continue to be monitored for safety and efficacy including best overall response and duration of response.

Gracell will also present as an oral abstract presentation the updated results from this IIT evaluating GC012F for the treatment of RRMM patients at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress. For more information on the study, please visit ClinicalTrials.gov using the identifier: NCT04236011.

Details of the ASCO (Free ASCO Whitepaper) presentation follow below:

2022 ASCO (Free ASCO Whitepaper) Annual Meeting

Abstract title: Updated results of a multicenter first-in-human study of BCMA/CD19 dual-targeting FasTCAR-T GC012F for patients with relapsed/refractory multiple myeloma (RRMM)
Abstract number: 8005
Session title: Hematologic Malignancies – Plasma Cell Dyscrasia
Presentation time: Sunday, June 5 at 9:36 AM CT
Presentation location: S406
About GC012F

GC012F is a FasTCAR-enabled dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma and B-cell non-Hodgkin’s lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.

About FasTCAR

CAR-T cells manufactured on Gracell’s proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next-day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, and, together with fast turnaround time, enables enhanced accessibility of cell therapies for cancer patients.

On May 26, 2022 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 a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting (Press release, Oncternal Therapeutics, MAY 26, 2022, View Source [SID1234615160]). In the CIRLL study, zilovertamab, an investigational anti-ROR1 monoclonal antibody, is being evaluated in combination with ibrutinib in patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). The clinical trial is being conducted in collaboration with the University of California San Diego (UC San Diego) and has been partially funded by the California Institute for Regenerative Medicine (CIRM).

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!

The updated interim data will be presented as a poster discussion session at the Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia session on Saturday, June 4, 2022 as part of the ASCO (Free ASCO Whitepaper) 2022 Annual Meeting:

Poster Title: Phase 1/2 study of zilovertamab and ibrutinib in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL)
Abstract Number: 7520
Session Name: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Session Date and Time: June 4, 2022 from 8:00-11:30 am (Central Time)
"The interim data update presented today further strengthens our confidence in the significant clinical value the combination of zilovertamab and ibrutinib can deliver to MCL and CLL patients. Solid objective response rate (ORR) of 85% and median progression-free survival (PFS) of 36 months in heavily pre-treated MCL patients in our CIRLL study support our Phase 3 registrational study ZILO-301, which we plan to initiate in the third quarter," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "We continue to be especially intrigued by the encouraging and robust response rate across multiple populations of high-risk MCL and CLL patients, most notably the prolonged PFS seen for those that express the p53 mutation, a particularly challenging population for BTK inhibitors. This is further proof that the combination is very active, and we believe it may address important unmet medical needs in difficult-to-treat patients with aggressive forms of hematological malignancies."

The results that will be presented in poster form and reviewed in a poster discussion at the ASCO (Free ASCO Whitepaper) 2022 Annual Meeting include 33 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 27 were evaluable for efficacy as of the April 8, 2022 data cut-off date.

Patients had high-risk factors and were heavily pre-treated at study entry, with 52% having a high Ki-67 proliferative index (≥30%), and 46% having an intermediate or high sMIPI prognostic score.
The ORR of 85% (23 of 27 evaluable patients) includes recently enrolled patients with relatively short follow-up time.
The complete response (CR) rate was 41% (11 of 27 evaluable patients). CRs have remained durable for up to 35 months.
The partial response (PR) rate was 44% (12 of 27 evaluable patients), and the stable disease (SD) rate was 7% (2 of 27 evaluable patients), for a total clinical benefit rate (CR, PR and SD) of 93%.
The ORR and median duration of response (DOR) were also favorable in patients with other high-risk features associated with disease difficult-to-treat with BTK inhibitors:
P53 mutation: ORR of 83%; median DOR of 13.8 months (95% CI: 11.9, NE), median PFS of 17.3 months (95% CI: 2.9, NE) and a landmark PFS over 80% at 15 months
Ki-67 ≥30%: ORR of 86%; median DOR not reached (95% CI: 13.7, NE)
>1 prior systemic therapy: ORR of 83%; median DOR not reached for patients receiving two prior lines of systemic therapy and 34 months (95% CI: 13.8, 34.1) for patients with ≥ 3 prior lines of systemic therapy
Prior treatment with ibrutinib: ORR of 80% (4/5), with two CRs, two PRs and one SD
Median PFS was 35.9 months for all patients with MCL after a median follow-up of 14.4 months (95% CI: 11.4, 19.3), regardless of number of prior systemic therapies. Further, median PFS had 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). Historical data in 20 patients with p53 mutation showed an ORR of 55% and median PFS of 4.0 months (Rule, 2019).
Thirty-four patients with CLL enrolled in the dose-finding and dose-confirming cohorts of this clinical trial (Part 1 & Part 2) as of the April 8, 2022 data cut-off date, were all evaluable for efficacy. Patients had high-risk factors, and most were heavily pre-treated at study entry, with 71% having RAI staging ≥2 and a median of two systemic prior therapies (range 1-9).

The ORR was 91% (31 of 34 evaluable patients).
The CR rate was 9% (3 of 34 evaluable patients).
The clinical benefit rate was 100%, with 28 of 34 (82%) evaluable patients achieving a PR, and three patients (9%) had SD.
The median PFS had not been reached for all patients with CLL, whether treatment-naïve or those with relapsed refractory disease.
Landmark PFS was 100% at 36 months for CLL patients with 1 or 2 prior lines of therapy, which compares favorably to historical ibrutinib monotherapy of ~ 73% (Byrd. 2019).
For patients with CLL who had received > 2 prior lines of therapy, the landmark PFS was over 85% at 24 months and 70% at 36 months, which compares favorably to the historical ibrutinib monotherapy landmark PFS at 24 and 36 months of ~ 65% and ~ 50%, respectively (Byrd. 2019).
Thirty-one patients with CLL have also been enrolled in the randomized efficacy cohort of this clinical trial (Part 3), of which 23 were evaluable for efficacy. Data on this cohort are maturing. The median PFS had not been reached for either group as of the April 8, 2022 cut-off date after 24 months of follow up.

The combination of zilovertamab plus ibrutinib has been well tolerated, with treatment emergent adverse events consistent with those reported for ibrutinib alone. There have been no dose-limiting toxicities and no serious adverse events attributed to zilovertamab alone. In patients with MCL, Grade 3-4 neutrophil decrease was documented in 9.1% of patients with zilovertamab plus ibrutinib, compared to 29% for ibrutinib alone from its registration study.

About the CIRLL Clinical Trial
The CIRLL clinical trial (CIRM-0001) is a Phase 1/2 trial evaluating zilovertamab 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 MCL and randomized Phase 2 cohort in CLL has been completed. An additional dose-expansion cohort of up to 10 patients with marginal zone lymphoma (MZL) has recently been added. Enrollment is expected to begin in Q2 2022. Additional information about the CIRM-0001 clinical trial and other clinical trials of zilovertamab may be accessed at ClinicalTrials.gov.

About Zilovertamab
Zilovertamab (formerly designated cirmtuzumab) is an investigational, humanized, potentially first-in-class monoclonal antibody targeting Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1). Zilovertamab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of patients with MCL, chronic lymphocytic leukemia (CLL) or MZL, 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, a Phase 1b clinical trial for patients with metastatic castration-resistant prostate cancer (mCRPC), and a Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, for patients with relapsed/refractory CLL. Both are open for enrollment.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen, not usually expressed on adult cells, but 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 inhibiting ROR1-expressing tumors. This led to the development of zilovertamab which binds this critical epitope of ROR1, highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when zilovertamab 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 zilovertamab for the treatment of patients with MCL and CLL/small lymphocytic lymphoma. Zilovertamab is in clinical development and has not been approved by the FDA for any indication.