On June 4, 2021 Daiichi Sankyo Company, Limited reported that New data from patritumab deruxtecan (HER3-DXd), a HER3 directed antibody drug conjugate (ADC), demonstrated preliminary evidence of clinically meaningful and durable tumor response in patients with locally advanced or metastatic TKI-resistant, EGFR-mutated non-small cell lung cancer (NSCLC) (Press release, Daiichi Sankyo, JUN 4, 2021, View Source [SID1234583581]).

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These extended follow-up data from the dose escalation portion and one expansion cohort of a phase 1 study of patritumab deruxtecan were presented today during an oral presentation (Abstract #9007) at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO21) Virtual Scientific Program.

While the efficacy of targeted therapy with EGFR TKIs is well-established in the treatment of patients with advanced EGFR-mutated NSCLC, the development of a broad range of resistance mechanisms commonly leads to disease progression.1,2 Subsequent salvage therapies after EGFR TKI and platinum-based chemotherapy have limited efficacy with progression-free survival (PFS) of approximately 2.8 to 3.2 months.2 New treatment approaches are needed to overcome resistance and improve survival in these patients.

An objective response rate (ORR), as assessed by blinded central review, was 39% (CI 95%; 26-52%) in 57 evaluable patients treated with patritumab deruxtecan (5.6 mg/kg). One confirmed complete response and 21 partial responses were observed. The disease control rate was 72% (CI 95%; 59-83%). After a median follow-up of 10.2 months (range, 5.2-19.9 months), the estimated median duration of response was 6.9 months (CI 95%; range, 3.1-NE months) and the estimated median PFS was 8.2 months (CI 95%; range, 4.4-8.3 months). Confirmed responses were observed in patients across a spectrum of baseline tumor HER3 membrane expression levels, EGFR activating mutations and EGFR TKI resistance mechanisms, including EGFR activating mutations (Ex19del, L858R, G719Y), other EGFR mutations (T790M, C797S, Ex20ins), amplifications (EGFR, CCNE1, MET) and non-EGFR mutations and fusions (MET, KRAS). A subgroup of patients treated with osimertinib and platinum-based chemotherapy (n=44) prior to enrollment in the study demonstrated similar efficacy. An ORR of 39% (CI 95%; 24-55%) and PFS of 8.2 months (CI 95%; 4.0-NE) was observed in this subgroup. Additionally, the confirmed ORR and median PFS were similar in patients with or without a history of brain metastases.

"EGFR TKIs are the standard of care for patients with advanced EGFR-mutated NSCLC. However, the activity of these agents is limited by the development of acquired resistance mechanisms," said Pasi A. Jänne, MD, PhD, Director, Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute. "In this study, where patients were heavily pre-treated, efficacy was observed in patients with and without known EGFR TKI resistance mechanisms in a population that is often difficult to treat. Targeting HER3 with patritumab deruxtecan may be a novel and promising strategy, and we look forward to further evaluating clinical activity and safety in the pivotal HERTHENA-Lung01 trial."

The safety profile of patritumab deruxtecan in patients treated with the 5.6 mg/kg dose (n=57) is consistent with that seen across all patients (n=81) in both the dose escalation and dose expansion cohort 1 of the study (doses range from 3.2 to 6.4 mg/kg). Grade 3 or higher treatment emergent events (TEAEs) occurred in 64% of all patients (n=81). TEAEs grade 3 or higher severity occurring in ≥ 5% of all patients were platelet count decreased, neutrophil count decreased, fatigue, anemia, dyspnea, febrile neutropenia, hypoxia, white blood cell count decreased, hypokalemia and lymphocyte count decreased. There were four cases of treatment-related interstitial lung disease (ILD) reported, as determined by an independent adjudication committee, including two of grade 1 severity, one grade 2, and one grade 3. The median time to adjudicated onset of treatment-related ILD was 53 days (range, 13-130 days). There were five TEAEs associated with death including two cases of disease progression, two cases of respiratory failure and one case of shock. All TEAEs associated with death were considered not related to the study drug.

"Treatment options that provide meaningful therapeutic benefit for patients with EGFR-mutated non-small cell lung cancer with disease progression following standard treatment with EGFR TKIs and platinum-based chemotherapy are limited," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "HER3 represents a novel target for therapeutic development as it is broadly expressed in non-small cell lung cancer. These results are encouraging since the safety profile was consistent with previous findings and response to patritumab deruxtecan was seen irrespective of the level of HER3 expression or mechanism of resistance to prior therapies."

Patients receiving 5.6 mg/kg (n=57) of patritumab deruxtecan were pre-treated with a median of four prior lines of therapy (range, 1-9), including EGFR TKIs (100%), platinum-based chemotherapy (91%) and immunotherapy (40%). A majority (86%) were previously treated with osimertinib. Of the 57 patients, 27 patients had brain metastases at baseline. As of data cut-off on September 24, 2020, 32% of patients remain on treatment with patritumab deruxtecan.

Summary of Results

Efficacy Measure

HER3-DXd Dose Escalation 5.6 mg/kg
Plus Dose Expansion 5.6 mg/kg (n=57) iv

Prior TKI±PBC
(n=57)

Prior OSI and PBC
(n=44)

ORR (%) (95% CI) i, ii

39% (26-52)

39% (24-55)

CR (%)

2%

2%

PR (%)

37%

36%

SD (%)

33%

30%

PD (%)

16%

18%

NE (%)

12%

14%

DCR (%) (95% CI)iii

72% (59-83)

68% (52-81)

Time to response (months)

2.6 months (1.2-5.4)

2.7 months (1.2-5.4)

Median DOR (months) (95% CI)

6.9 months (3.1-NE)

7.0 months (3.1-NE)

Median PFS (months) (95% CI)

8.2 months (4.4-8.3)

8.2 months (4.0-NE)

CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; OSI, osimertinib; NE, not estimable; PBC, platinum-based chemotherapy; PD, progressive disease; PR, partial response; PFS, progression-free survival; SD, stable disease; TKI; tyrosine kinase inhibitor
i As assessed by independent central review
ii ORR is (CR + PR)
iii DCR is (CR + PR + SD)
iv Median follow up: 10.2 (range, 5.2-19.9) months

About the Phase 1 Non-Small Cell Lung Cancer Study

The global, multicenter, open label, two-part phase 1 study is evaluating patritumab deruxtecan in previously treated patients with metastatic or unresectable NSCLC.

The dose escalation part of the study evaluated patients with EGFR-mutated disease either with progression on osimertinib or T790M-negative after progression on erlotinib, gefitinib or afatinib. The primary objective of this part of the study was to assess the safety and tolerability of patritumab deruxtecan and determine the recommended dose for expansion (RDE).

The dose expansion part of the study is evaluating patritumab deruxtecan at the RDE (5.6 mg/kg every three weeks) in three cohorts. Cohort 1 includes patients with locally advanced or metastatic EGFR-mutated NSCLC who experienced disease progression after taking one or more EGFR TKIs and one or more platinum based chemotherapy regimens. Cohort 2 includes patients with squamous or non-squamous NSCLC without EGFR-activating mutations following platinum-based chemotherapy and following an anti-PD-1 or anti-PD-L1 antibody regimen. Cohort 3 includes patients with NSCLC with EGFR-activating mutations including any histology other than combined small cell and non-small cell lung cancer; patients in Cohort 3 are randomized 1:1 to receive the 5.6 mg/kg RDE regimen (Cohort 3a) or an escalating up-titration regimen of patritumab deruxtecan (Cohort 3b).

Preliminary data from the dose escalation part of the study were presented previously at the 2019 World Conference on Lung Cancer, and early data from the dose escalation part (5.6 mg/kg dose) and Cohort 1 of the dose expansion were presented at the 2020 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress. Exploratory biomarker analyses assessing genomic alterations of patient tumors were presented at the 2020 World Conference on Lung Cancer.

The primary objective of the dose expansion part of the study is to assess efficacy of patritumab deruxtecan as measured by confirmed objective response rate assessed by blinded independent central review. Secondary study endpoints include investigator-assessed objective response rate; safety, tolerability and preliminary efficacy; and characterization of the pharmacokinetics of patritumab deruxtecan. The study enrolled patients at multiple sites in the U.S., Europe, Japan and other countries in Asia. For more information, visit ClinicalTrials.gov.

About Non-Small Cell Lung Cancer

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. There were an estimated 2.2 million new cases of lung cancer and 1.8 million deaths in 2020.3 Most lung cancers are diagnosed at an advanced or metastatic stage.4 Non-small cell lung cancer (NSCLC) accounts for 80 to 85% of all lung cancers.5

The introduction of targeted therapies and checkpoint inhibitors in the past decade has improved the treatment landscape for patients with advanced or metastatic NSCLC; however, the prognosis is particularly poor among patients who have progressed after treatment with standard therapies. For patients who are not eligible for current treatments, or whose cancer continues to progress, new therapeutic approaches are needed.6

The mutationally-activated EGFR tyrosine kinase is a well-established oncogenic driver and molecular target for management of advanced stage NSCLC.7 For patients with advanced EGFR-mutated NSCLC, targeted therapy with EGFR TKIs offer higher response rates and progression-free survival compared to chemotherapy.7 However, most patients eventually develop resistance to these therapies, and standard treatment options are limited.8 Treatment options used in this setting historically have demonstrated limited efficacy with progression free survival of up to 6.4 months for platinum-based chemotherapy and 3.2 months for other salvage therapies.3,9 New treatment approaches are needed to overcome resistance and improve survival in these patients.

About HER3

HER3 is a member of the EGFR family of receptor tyrosine kinases, which are associated with aberrant cell proliferation and survival.10 Approximately 25 to 30% of lung cancers worldwide have an EGFR-activating mutation, and it is estimated that about 83% of all NSCLC tumors express the HER3 protein, which can be associated with an increased incidence of metastases, reduced survival and resistance to standard of care treatment.11,12,13 Currently, no HER3 directed medicines are approved for the treatment of cancer.

About Patritumab Deruxtecan

Patritumab deruxtecan (HER3-DXd) is one of three lead DXd ADCs in the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, patritumab deruxtecan is comprised of a human anti-HER3 antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Patritumab deruxtecan is currently being evaluated in a comprehensive development program across multiple cancers as both a monotherapy and in combination with other anticancer treatments. The development program includes HERTHENA-Lung01, a pivotal phase 2 study in patients with locally advanced or metastatic EGFR-mutated NSCLC previously treated with a TKI and platinum-based chemotherapy; a phase 2 study in patients with advanced/metastatic colorectal cancer with disease progression following at least two prior lines of systemic therapy; a phase 1/2 study in HER3 expressing metastatic breast cancer; a phase 1 study in combination with osimertinib in locally advanced/metastatic EGFR-mutated NSCLC; and, a phase 1 study in previously treated patients with metastatic or unresectable NSCLC.

Patritumab deruxtecan is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.

On June 4, 2021 The US Oncology Network (The Network), US Oncology Research and Ontada reported that Results from the first phase of the broad, collaborative MYLUNG Consortium research study in metastatic non-small cell lung cancer (mNSCLC) were released at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, US Oncology, JUN 4, 2021, View Source [SID1234583599]). The findings provide a close-up look at current biomarker testing rates and turnaround times for patients with mNSCLC treated in community practices within The Network. Most notably, Protocol 1 findings show that there are barriers that must be addressed as more than 80 percent of NSCLC is detected at Stage 4 and median time from diagnosis to first-line therapy is about five weeks.

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"The pace and development of treatments in non-small cell lung cancer is dramatic," said Makenzi Evangelist, MD, principal investigator for the MYLUNG Consortium’s Protocol 2 and oncologist with New York Oncology Hematology (NYOH), a practice in The Network. "There are already several targeted therapies to treat subsets of populations, and many more are in the pipeline that hold incredible potential. Unfortunately, barriers exist that prevent the necessary comprehensive biomarker testing that enables the use of these treatments. The MYLUNG Consortium study will be invaluable in identifying these obstacles and developing practical interventions that will allow us to fulfill the promise of precision medicine for patients with this difficult cancer."

Dr. Evangelist presented the findings during an oral presentation at ASCO (Free ASCO Whitepaper) titled, "Biomarker tissue journey among patients with untreated metastatic non-small cell lung cancer (mNSCLC) in The US Oncology Network community practices." (ASCO Abstract 9004).

The MYLUNG Consortium is a collaborative and innovative research study comprised of three protocols over a five-year period. Protocol 1, which was just completed, is a retrospective study of more than 3,500 patients with mNSCLC that investigated the following areas: testing rates for ALK, BRAF, EGFR, ROS1, and PD-L1 mutations; use of the full next-generation sequencing panel (NGS); time from NSCLC diagnosis to first-line therapy; turnaround times from biomarker orders to results; and time from NSCLC diagnosis to test results.

"We have derived significant insights from the study data so far," noted Sarah Alwardt, PhD, vice president of Operations for Ontada. "We are now able to see where there are gaps regarding targeted therapy. This real-world study showed that while most patients had at least one biomarker test result available prior to first-line therapy, less than 50 percent had five or more biomarkers tested. Consequently, a large percentage of patients were not given the opportunity for a targeted therapy."

Additionally, the median time from diagnosis to first-line therapy was about five weeks, a concern for patients anxiously waiting for treatment. Turnaround time from testing orders to results was about two weeks, indicating the need to get test results to physicians sooner so they have all critical information in front of them during development of the treatment plan. Next Generation Sequencing testing improved over time, suggesting comprehensive testing is increasing. Most of the population was diagnosed at advanced disease, with roughly over 80 percent detected at stage 4.

"Protocol 1 provides a look at what was happening retrospectively based on clinical data abstraction, allowing us to draw some early conclusions about historical baseline trends for testing patterns," noted Robert L. Coleman, MD, FACOG, FACS, chief scientific officer of US Oncology Research and the MYLUNG Consortium program principal investigator. "Retrospective studies like this help us understand where we are as far as testing behaviors, while also identifying gaps in the data that need to be filled with the prospective research the MYLUNG Consortium will address in the next protocols."

Data from Protocol 1 will be compared to the next phase of the MYLUNG Consortium study, Protocol 2, which will evaluate contemporary ordering practices and turnaround times prospectively. It will enroll about 1,000 patients from approximately 11 sites and will monitor the real-world patient journey from presentation through their first line of cancer therapy, focusing on how diagnostic biomarker information is obtained, utilized and operationalized in decision-making. Patients are currently being enrolled in this stage of the study.

The final phase of the study, Protocol 3, will serve as a platform upon which prospectively assessed interventional strategies in patient-engagement algorithms will be conducted. Up to 7,500 patients from approximately 20 participating sites will be recruited over a five-year period. Individual clinical trials will integrate findings from the previous protocols and explore new processes and associated outcomes. The goal is to help providers make the best treatment recommendations based on the data available while improving access to testing and appropriate therapies for patients with mNSCLC.

The MYLUNG Consortium study is enabled through a unique collaboration of various organizations and stakeholders working together across the spectrum of NSCLC drug development, therapy and care. The number of consortium participants continues to grow, all bringing unique perspectives to this innovative study. It brings together providers and researchers in The Network, US Oncology Research and Ontada with life sciences companies Amgen, AstraZeneca, Eli Lilly and Company, Genentech (a member of the Roche Group), and Mirati Therapeutics, Inc. Patient advocacy groups LUNGevity and GO2 Foundation for Lung Cancer are also participating, playing a key role in the study by keeping the focus on patients. Healthcare provider members include Illinois Cancer Specialists, Maryland Oncology Hematology, Minnesota Oncology, New York Oncology Hematology, Oncology Hematology Care, Rocky Mountain Cancer Centers, Southern Cancer Center, Virginia Cancer Specialists, Virginia Oncology Associates, Willamette Valley Cancer Institute and Research Center and Woodlands Medical Specialists.

Read more about the MYLUNG Consortium here. To schedule a media interview with one of the study investigators, contact Claire Crye at [email protected].

On June 4, 2021 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that the Company has entered into an additional collaborative agreement with NextGenNK Competence Center-associated research groups at the Department of Medicine, Huddinge, Karolinska Institutet ("KI") in Stockholm, Sweden, aimed at producing novel cell-based therapeutics using natural killer ("NK") cells derived from induced pluripotent stem cells ("iPSCs") (Press release, Sorrento Therapeutics, JUN 4, 2021, View Source [SID1234583901]). Sorrento and KI are collaborative partners in the Competence Center for the development of next-generation NK cell-based cancer immunotherapies ("NextGenNK") coordinated by KI.

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Under the agreement, Sorrento will provide know-how in the core chimeric antigen receptor ("CAR") and dimeric antigen receptor ("DAR") technologies and support the collaborative effort to develop new CAR-NK and DAR-NK candidates, as well as fund the translational validation of the technologies. Multiple product candidates will be developed and tested in the initial phase of the planned work, with the goal that the candidate products will qualify for further human clinical trials.

The foundational Sorrento research assets critical to this program are novel proprietary CAR and DAR constructs identified through Sorrento’s proprietary G-MAB fully human antibody library and previously validated as determinants of cell-based therapy potency against hematologic and solid tumors.

"It is a privilege to continue and extend our collaborative work with the distinguished KI faculty. We are proud to contribute our technologies to produce new optimized off-the-shelf adoptive NK cell immunotherapies", said Dr. Henry Ji, Chairman and CEO of Sorrento. "Our partnership with KI combines our know-how with the expertise of a world-renowned institution in the field of NK cell therapy. These types of partnerships are essential in advancing medicine and bringing new solutions to cancer patients in need."

KI scientists within NextGenNK will establish iPSC-derived NK-based therapeutic candidates utilizing Sorrento’s constructs and DAR technology. Work within KI has contributed to the development of methodologies that consistently generate robust and potent NK cell lineages following iPSC differentiation. Clinical trials of NK cell-based therapies for treatment of multiple myeloma led by researchers at KI have yielded promising preliminary results with long-lasting remissions. In a very cross-knit collaboration between Sorrento and KI, the team will aim to establish novel allogeneic, off-the-shelf, retargeted NK cell-based therapies.

Utilizing iPSCs enables mass production of off-the-shelf NK cell therapies that leverage Sorrento’s existing manufacturing infrastructure and know-how. Sorrento expects these validated re-engineered NK cell-based therapeutic candidates could potentially become a new generation in off-the-shelf treatments for cancer and infectious diseases. The core research will be performed at Karolinska Institutet with active involvement of the Sorrento R&D team in San Diego.

"The present collaboration brings together key competence from Sorrento and KI in an important area of cancer immunotherapy research. Sorrento’s intellectual contribution to the research at the Competence Center is a critical piece in enabling retargeted off-the-shelf NK cell products", said Evren Alici, Principal Investigator at KI.

"This is an important step in further enabling academic and industrial partnerships in the mission of achieving common goals for advancement of novel cancer immunotherapies," said Hans-Gustaf Ljunggren, Director of the NextGenNK Competence Center.

On June 4, 2021 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery and development of drugs for the treatment of cancer, reported a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting (Press release, Cellectar Biosciences, JUN 4, 2021, View Source [SID1234583516]). In conjunction with the poster presentation, management will host a KOL call with the lead investigator for the company’s Phase 2 CLOVER-1 study of CLR 131 in patients with relapsed/refractory B-cell hematologic cancers, Dr. Sikander Ailawadhi, M.D. of the Mayo Clinic.

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The poster presentation entitled: Treatment Free Remission (TFR) and Overall Response Rate (ORR) Results in Patients with Relapsed/Refractory Waldenstrom’s Macroglobulinemia (WM) Treated with CLR 131 is an in-depth update of six patients from the company’s Phase 2a study of CLR 131 in Waldenstrom’s macroglobulinemia. To date, data have shown:

100% (6/6) overall response rate, 83.3% (5/6) major response rate and a 16.7% (1/6) complete response rate
Median time to initial response was 22 days after first infusion
Median time to major response, as defined as at least a 50% reduction in IgM, was 44 days after first infusion
Mean treatment free remission, as defined as the time from the last CLR 131 infusion to progression of disease, is 1.1 years and remains ongoing
Duration of response has not been reached, with 100% of the MYD88 wild type and high risk patients exceeding 8.5 months
Progression free survival (PFS) for both MYD88 wild type patients as well as the high-risk subgroup has not been reached after 18 months; PFS for multidrug refractory patients was 11 months
The most frequently reported treatment emergent adverse events were cytopenias
"CLR 131 is a differentiated targeted radiotherapy that has the potential to address patients with any mutational status, risk profile or multi-drug refractoriness in WM. Our pivotal study strategy will leverage these properties to address the treatment needs of patients, including the potential to provide durable response rates and meaningful treatment-free remission," said Dr. John Friend, chief medical officer at Cellectar. "CLR 131 has demonstrated impressive results including, to our knowledge, the only monotherapy to result in a complete response in this challenging WM patient set."

James Caruso, president and CEO of Cellectar added, "The data presented today from our ongoing Phase 2 CLOVER-1 study of CLR 131 in Waldenstrom’s further validates our clinical development program and gives us confidence in our goal of providing a new and better treatment with the potential to prolong and improve the quality of life for patients suffering from this devastating disease."

Management will host a conference call and webcast today, June 4, at 10:00 am ET featuring key opinion leader Dr. Sikander Ailawadhi. Dr. Ailawadhi is a Professor of Medicine, Lead, International Cancer Center, Division of Hematology/Oncology, Departments of Medicine and Cancer Biology at Mayo Clinic Florida. He was awarded the 2013 NCI Cancer Clinical Investigator Team Leadership Award as an Assistant Professor of Medicine at the USC Norris Comprehensive Cancer Center. Subsequently, he joined the Division of Hematology and Oncology at Mayo Clinic in Florida as a Senior Consultant in order pursue his career goal of clinical, translational and outcomes-based research in B-cell malignancies.

A replay of the call will be available on the Events page of company website following the live event.

About the Pivotal Trial of CLR 131 in Waldenstrom’s macroglobulinemia (WM)
The pivotal trial is designed as a global, non-comparator, single arm, expansion cohort of the currently ongoing Phase 2 CLOVER-1 study of CLR 131. The study will enroll 50 WM patients. Patients in the trial will receive up to four doses of CLR 131 over two cycles (cycle one days 1, 15, and cycle two days 57, 71). The primary endpoint of the trial is response rate as defined as a partial response (a minimum of a 50% reduction in the biological marker IgM) or better in patients that receive a minimum total body dose of 60 mCi with secondary endpoints of treatment free survival, duration of response and progression free survival. An independent data monitoring committee (iDMC) will perform an interim safety and futility evaluation on the first 10 patients enrolled. The assessment will occur patient by patient and will conclude after the tenth patient is evaluated; there is no planned study stoppage.

About Waldenstrom’s macroglobulinemia
Waldenstrom’s macroglobulinemia (WM) is a rare and incurable disease defined by specific genotypic subtypes that defines patient responses and long-term outcomes. The annual incidence is 6,500 with prevalence of approximately 60,000 patients globally. WM is a lymphoma, or cancer of the lymphatic system. The disease occurs in a type of white blood cell called a B-lymphocyte or B-cell, which normally matures into a plasma cell whose job is to manufacture immunoglobulins (antibodies) to help the body fight infection. In WM, there is a malignant change to the B-cell in the late stages of maturing, and it continues to proliferate into a clone of identical cells, primarily in the bone marrow but also in the lymph nodes and other tissues and organs of the lymphatic system. These clonal cells over-produce an antibody of a specific class called IgM.

WM cells have characteristics of both cancerous B-lymphocytes (NHL) and plasma cells (multiple myeloma), and they are called lymphoplasmacytic cells. For that reason, WM is classified as a type of non-Hodgkin’s lymphoma called lymphoplasmacytic lymphoma (LPL). About 95% of LPL cases are WM; the remaining 5% do not secrete IgM and consequently are not classified as WM.

There is no standard treatment for WM. Several drugs have demonstrated activity either alone or in combinations, but only a single drug has received regulatory approval. Treatment is mainly focused on the control of symptoms and the prevention of organ damage. Front-line treatments for WM include rituximab alone or in combination with other agents. In the salvage therapy (second line or later) setting, ibrutinib, combinations of proteosome inhibitors and immunomodulatory drugs and stem cell transplantation are considered. Ibrutinib is the only drug to receive regulatory approval (2015) as a salvage therapy; in late 2019, it was approved for front-line treatment in combination with rituximab. Factors such as long-term cytopenias, age, hyper viscosity, the need for quick disease control, lymphadenopathy, co-morbidities, and IgM-related end-organ damage are key consideration in the choice of treatment.

On June 4, 2021 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, reported that updated data from the Company’s Phase 1 study of TJ004309 and Tecentriq (atezolizumab) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) virtual annual meeting (Press release, Tracon Pharmaceuticals, JUN 4, 2021, View Source [SID1234583534]).

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In poster presentation 2511 entitled, "The safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of uliledlimab (TJ004309), a differentiated CD73 antibody, in combination with atezolizumab in patients with advanced cancer," data were presented from 20 refractory cancer patients with advanced or metastatic solid tumors treated with the combination of uliledlimab and atezolizumab.

Key results included:

Uliledlimab was safe and well-tolerated up to 20 mg/kg every three weeks (Q3W) and 15 mg/kg once weekly (QW) as a monotherapy and in combination therapy with atezolizumab 1200 mg Q3W. No dose limiting toxicity was observed and the maximum tolerated dose was not reached.
Full saturation of circulating and cell-bound CD73 was achieved at doses ≥ 10 mg/kg.
Linear PK profile was observed at the doses ≥10 mg/kg following a single dose and the PK profile of uliledlimab supports Q3W dosing.
There was evidence of clinical activity (one complete response, two partial responses and three cases of stable disease) in both PD-(L)1 treatment naïve and refractory cancer patients, following treatment with uliledlimab and atezolizumab.
Higher tumor CD73 and PD-L1 co-expression were found in responders compared to non-responders.
"Uliledlimab was safe and refractory solid tumor patients benefitted following treatment with uliledlimab and atezolizumab," said Francisco Robert M.D., lead author and Professor of Medicine at the University of Alabama, Birmingham. "Further evaluation of uliledlimab in combination with checkpoint inhibitors in lung and ovarian cancers is warranted."

The poster is available on TRACON’s website at www.traconpharma.com.

About TJ004309

TJ004309 is a novel, humanized antibody discovered by I-Mab, against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine, which is highly immunosuppressive. TRACON is developing TJ004309 in collaboration with I-Mab Biopharma through one of our two strategic agreements with them, whereby we are responsible for the regulatory and clinical development of TJ004309 in the U.S. and Europe for this study. TJ004309 is currently being studied in an ongoing Phase 1 trial to assess safety and preliminary efficacy as a single agent and when combined with the PD-L1 checkpoint inhibitor Tecentriq in patients with advanced solid tumors.