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 Exelixis, Inc. (NASDAQ: EXEL) reported results from a post-hoc analysis of the phase 3 CheckMate -9ER trial demonstrating that CABOMETYX (cabozantinib) in combination with Bristol Myers Squibb’s OPDIVO (nivolumab) resulted in a statistically significant and clinically meaningful increase in quality-adjusted survival compared with sunitinib for patients with previously untreated advanced renal cell carcinoma (RCC) (Press release, Exelixis, JUN 4, 2021, View Source [SID1234583515]). The quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) data will be presented as part of the Poster Session: Health Services Research and Quality Improvement at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held virtually, June 4-8, 2021. All posters will be available on demand beginning at 6:00 a.m. PT on Friday, June 4.

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"Physicians must balance efficacy, safety and quality-of-life considerations when recommending treatment for patients with advanced kidney cancer; longer survival alone is not enough if the quality of life during that time is poor," said David Cella, Ph.D., the Ralph Seal Paffenbarger Professor and chair of the Department of Medical Social Sciences at the Northwestern University Feinberg School of Medicine and presenting author. "This analysis shows that the overall survival benefit demonstrated in the phase 3 CheckMate -9ER trial results in clinically important gains in quality-adjusted survival. For this community, time with relatively good health can be an important factor in treatment decisions, and these results offer both patients and physicians a fuller picture of the clinical benefits of the combination of cabozantinib and nivolumab."

The Q-TWiST metric combines the quantity and quality of time patients spend in each of the following three states: time without symptoms of disease or toxicity before progression (TWiST), time with any grade 3 or 4 adverse events after randomization and before progression or censoring and time after disease progression until death. In the intent-to-treat population (n = 651) in this post-hoc analysis, patients treated with CABOMETYX in combination with OPDIVO had a Q-TWiST gain of 4.0 months (95% confidence interval [CI]: 2.4-5.7) compared with patients treated with sunitinib. The resulting relative gain of 16.9% is considered "clearly clinically important" (defined as a gain of at least 15% based on published minimally important difference norms).

Most gains were driven by added time in relatively good health (TWiST) (4.7 months; 95% CI: 2.9-6.7) for CABOMETYX in combination with OPDIVO compared with sunitinib. Time with any grade 3/4 adverse events was 0.5 months longer (95% CI: 0.1-0.9) with CABOMETYX in combination with OPDIVO than with sunitinib. Time after disease progression until death was 2.0 months longer (95% CI: 0.1-4.1) with sunitinib than with CABOMETYX in combination with OPDIVO.

"There is a need for additional first-line advanced kidney cancer treatments that demonstrate quality-of-life improvements as well as efficacy benefits, and this analysis along with the patient-reported outcomes from CheckMate -9ER presented earlier this year add to the clinical evidence supporting the use of CABOMETYX in combination with OPDIVO," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "These are important findings that reinforce our efforts to bring treatment options to patients that may offer an improved quality of life while on therapy."

About CheckMate -9ER

CheckMate -9ER is an open-label, randomized (1:1), multi-national phase 3 trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma with a clear cell component. A total of 651 patients (22% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to CABOMETYX at a dose of 40 mg QD and OPDIVO (n = 323) versus sunitinib (n = 328). The primary endpoint is PFS. Secondary endpoints include OS and ORR. The primary efficacy analysis compares the doublet combination regimen of CABOMETYX and OPDIVO versus sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co. and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About RCC

The American Cancer Society’s 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common form of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.1 Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021.3

About 70% of RCC cases are known as "clear cell" carcinomas, based on histology.4 The majority of clear cell RCC tumors have below-normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with OPDIVO. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

On June 4, 2021 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that novel supportive data from the ongoing Phase I clinical trial with the 4-1BB (CD137) drug candidate ATOR-1017 developed as tumor-directed therapy for metastatic cancer (Press release, Alligator Bioscience, JUN 4, 2021, View Source [SID1234583508]). The results, presented in a poster presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, validate the therapeutic potential of ATOR-1017 demonstrating a very favorable safety profile combined with clear signs of proof of mechanism, as activation of T cells in the circulation was observed across active dose levels of ATOR-1017.

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"ATOR-1017 is the first of the second generation monospecific 4-1BB antibodies to report proof of mechanism by showing increase in number of activated T cells in the circulation. Safety data show that ATOR-1017 is safe and well tolerable at doses up to 200 mg and no dose limiting toxicity has occurred. We are encouraged by these data validating the potential of ATOR-1017. and we are now focused on completing the study and determining the dose for the subsequent Phase II program," said Søren Bregenholt, CEO of Alligator Bioscience.

The Phase I study with ATOR-1017 is a dose escalation study in patients with advanced solid cancer (NCT04144842). The primary endpoint of the study is to investigate the safety and tolerability of ATOR-1017 and to determine the recommended dose for subsequent Phase II studies. The first patient was dosed in December 2019. As of data cut-off March 31, 2021, a total of 13 patients with varying advanced solid malignancies had been included. 4 patients (31%) remained on treatment, 3 (23%) of whom had confirmed stable disease for a period of 3.5-12.5 months.

The results from the evaluation of doses up to and including 200 mg demonstrate that ATOR-1017 has an encouraging safety profile as the drug related adverse events in the study have generally been mild and transient. No dose-limiting toxicity or severe immune-related adverse events have been reported. The results further demonstrate that ATOR-1017 exhibits a favorable pharmacokinetic profile with linear elimination and no accumulation. Activation of T cells in the circulation was observed across therapeutic dose levels of ATOR-1017 demonstrating biological activity and proof of mechanism.

The ASCO (Free ASCO Whitepaper) poster presentation with the title "A first-in-human, multicenter, open-label, phase 1 study of ATOR-1017, a 4-1BB antibody, in patients with advanced solid malignancies" will be available at 03.00 p.m. CEST today, June 4, on the company website View Source

This information is such information as Alligator Bioscience AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 08:00 a.m. CEST on June 4, 2021.

On June 4, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported two trial in progress posters, on the Phase 1 INNATE clinical trial and the Phase 2 SELECT clinical trial, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting (Press release, Jounce Therapeutics, JUN 4, 2021, View Source [SID1234583507]). INNATE, a proof-of-concept (POC) trial, is evaluating Jounce’s lead macrophage program JTX-8064 (anti-LILRB2/ILT4 inhibitor) as a monotherapy and in combination with pimivalimab (anti-PD-1 inhibitor, formerly known as JTX-4014) in patients with a variety of advanced solid tumors. SELECT, Jounce’s second POC trial, is evaluating pimivalimab as a monotherapy and in combination with vopratelimab (ICOS agonist) in a novel biomarker selection paradigm in PD-(L)1 naïve non-small cell lung cancer patients.

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"Our INNATE trial is rapidly progressing through dose escalation and we are on-track to begin indication-specific, POC, monotherapy and pimivalimab combination expansion cohorts in the second half of this year," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "Furthermore, we are excited to announce the expansion cohort indications for INNATE, which were selected using our translational data-driven approach, linking JTX-8064’s mechanism to tumor types in three groups of patients including: PD-(L)1 inhibitor experienced and resistant, PD-(L)1 inhibitor naïve and historically resistant, and PD-(L)1 inhibitor and historically more sensitive. JTX-8064 is one of only two clinical-stage LILRB2 programs in development and we expect it to be the first program to initiate expansion cohorts in four of our chosen tumor types. We are also pleased to see TISvopra positivity rates tracking with expectations in our biomarker selection trial, SELECT, and we remain on-track to report data next year."

Poster Presentation Details:

Poster Title: Phase 1, First-in-Human trial of JTX-8064, an anti-LILRB2/ILT4 monoclonal antibody, as monotherapy and in combination with anti-PD-1 in adult patients with advanced solid (INNATE)
Presenter: Kyriakos P. Papadopoulos, MD, South Texas Accelerated Research Therapeutics (START), San Antonio, TX
Session Title: Developmental Therapeutics – Immunotherapy
Abstract Number: TPS2672
Date and Time: Friday, June 4, 2021; 9:00am ET
Highlights from the trial in progress poster include the selection criteria for expansion cohorts in the ongoing Phase 1 INNATE trial and an outline the future biomarker plan:

Expansion cohort selection was informed using human histoculture and gene signature analysis from Jounce’s Translational Science Platform and includes PD-(L)1 naïve and experienced patients as well as PD-(L)1 sensitive and resistant tumor types.
The INNATE trial is divided into 4 stages with indication-specific expansion cohorts intended to establish proof-of-concept for JTX-8064:
JTX-8064 monotherapy dose escalation in relapsed / refractory solid tumors
JTX-8064 plus pimivalimab dose escalation in relapsed / refractory solid tumors
JTX-8064 monotherapy expansion in PD-(L)1i naïve platinum resistant ovarian cancer
JTX-8064 plus pimivalimab expansions in:
PD-(L)1i naïve platinum resistant ovarian cancer
PD-(L)1i naïve head and neck squamous cell carcinoma (HNSCC)
PD-(L)1i naïve undifferentiated pleomorphic sarcoma (UPS) and liposarcoma (LPS)
PD-(L)1i experienced non-small cell lung cancer (NSCLC)
PD-(L)1i experienced clear cell renal cell carcinoma (ccRCC)
PD-(L)1i experienced triple negative breast cancer (TNBC)
PD-(L)1i experienced cutaneous squamous cell carcinoma (cSCC).
The dose for expansion cohorts will be selected based on safety, pharmacokinetic and receptor occupancy data from the monotherapy dose escalation stage of INNATE.
Archival and pre-treatment tumor biopsies as well as pre- and post-treatment blood samples will be collected to evaluate a number of potential predictive and pharmacodynamic biomarkers using Jounce’s Translational Science Platform.
Poster Title: Phase 2 Study of PD-1 Inhibitor JTX-4014 (Pimivalimab) Alone and in Combination with Vopratelimab, an ICOS Agonist, in Biomarker-selected Subjects with Metastatic NSCLC After One Prior Platinum-containing Regimen (SELECT)
Presenter: Oleh Kobziev, MD, Regional Center of Oncology, Kharkiv, 61070, Ukraine
Session Title: Lung Cancer – Non-Small Cell Metastatic
Abstract Number: TPS9137
Date and Time: Friday, June 4, 2021; 9:00am ET

The SELECT trial is currently enrolling approximately 75 immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker

TISvopra may serve as a unique biomarker for potential increased benefit for both pimivalimab monotherapy as well as pimivalimab in combination with vopratelimab.
Data from Jounce and a third-party ICOS agonist program support an ICOS-focused biomarker selection strategy to identify patients that may benefit from ICOS agonism.
Early screening data from SELECT support Jounce’s estimate that approximately 20% of PD-(L)1i naïve non-small cell lung cancer patients tested for TISvopra in the study would meet the TISvopra positivity threshold.
SELECT is on-track to report clinical data in 2022.
Both posters will be available on the "Our Pipeline" section of the Jounce Therapeutics website under "Publications" at www.jouncetx.com.

About JTX-8064

JTX-8064 is a humanized IgG4 monoclonal antibody designed to specifically bind to Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting and the 2019 and 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meetings support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical trial named INNATE (NCT04669899) of JTX-8064 as a monotherapy and in combination with Jounce’s internal anti-PD-1 inhibitor, pimivalimab (formerly JTX-4014) is currently enrolling patients with advanced solid tumors.

About Pimivalimab

Pimivalimab (formerly JTX-4014) is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Pimivalimab demonstrated a 17% durable overall response rate in a Phase 1 trial of 18 heavily pre-treated PD-(L)1 inhibitor naïve patients, which excluded all tumor types for which PD-(L)1 inhibitors were approved. In this Phase 1 trial, pimivalimab was shown to have an acceptable safety profile. Pimivalimab is currently being assessed in the INNATE Phase 1 trial (NCT04669899) in combination with JTX-8064, a LILRB2 (ILT4) inhibitor. Pimivalimab is also being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab, a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors.

About Vopratelimab

Vopratelimab is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Vopratelimab is currently being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with Jounce’s internal investigational PD-1 inhibitor, pimivalimab (formerly JTX-4014), compared to pimivalimab alone. The SELECT trial is currently enrolling approximately 75 immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor. SELECT is powered to demonstrate the statistical superiority of the combination of vopratelimab plus pimivalimab compared to pimivalimab.

On June 4, 2021 Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplants to more patients, reported additional positive results from a Phase 2 clinical trial of MGTA-145 and plerixafor in patients with multiple myeloma at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held virtually June 4-8, 2021 (Press release, Magenta Therapeutics, JUN 4, 2021, View Source [SID1234583506]).

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"We are very pleased to see continued favorable results for MGTA-145 and plerixafor for stem cell mobilization and collection in patients with multiple myeloma," said Jason Gardner, D.Phil., President and Chief Executive Officer, Magenta Therapeutics. "These results build on those previously disclosed from this study and the Phase 1 trials to further demonstrate MGTA-145 and plerixafor’s potential as a rapid, reliable, well-tolerated approach to stem cell mobilization and collection, which has positive implications for patients and donors."

Additional Results – MGTA-145 Multiple Myeloma Phase 2 Clinical Trial

The investigator-initiated, 25-patient Phase 2 clinical trial is designed to evaluate the ability of MGTA-145, in combination with plerixafor, to mobilize and collect hematopoietic stem cells for autologous stem cell transplant in patients with multiple myeloma. This study is led by Surbhi Sidana, M.D., Assistant Professor of Medicine in the Division of Blood and Marrow Transplantation and Cellular Therapy at Stanford University School of Medicine.

Previously reported results from this trial were announced on May 12, 2021, in a published abstract for the European Hematology Association (EHA) (Free EHA Whitepaper) Congress and provided preliminary data from the initial cohort of 10 patients.

Summary of cumulative results through data cut-off date:

All patients (15/15) have met the primary endpoint of mobilization and collection of 2 million CD34+ stem cells per kg in up to two days. Twelve of 15 patients achieved the primary endpoint in a single day of dosing and collection.
The median number of total CD34+ stem cells collected on day 1 and 2 (if needed) was 6.3 million per kg. Current standard of care with G-CSF-based regimens require a minimum of five days of dosing to initiate stem cell collection.
All transplanted patients to date (12/12) successfully engrafted, with median recovery of neutrophils after 12.5 days and platelets after 18 days, which are within transplant expectations in multiple myeloma.
Six patients have completed day-100 follow up, with demonstrated durable engraftment indicative of a successful transplant.
The collected CD34+ stem cells contain a high percentage (40%) of CD34+CD90+, a stem cell population associated with multi-lineage, long-term engraftment, an amount substantially greater than historically observed with G-CSF-mobilized cells.
The regimen of MGTA-145 and plerixafor was well tolerated. Acute, transient, MGTA-145-related grade 1 bone or musculoskeletal pain was observed in 40% of patients shortly after MGTA-145 infusion, resolving within 10 minutes for all patients, and none required pain medication or other intervention.
As indicated previously, this trial has broad and clinically representative inclusion criteria and includes patients that represent the general transplant-eligible population of patients with multiple myeloma. Patients enrolled in this trial included those patients with risk factors that could impact stem cell mobilization and collection, such as myeloma-directed therapies that are known to impact stem cell collection, previous malignancy treated with chemotherapy and/or radiation, and other co-morbid conditions. Mobilization agents may be less effective in patients with multiple risk factors. Final clinical data from this trial are anticipated by the end of 2021. MGTA-145 is also being evaluated for its ability to mobilize and collect stem cells from donors for allogenic transplant in patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in a Phase 2 trial, and an additional Phase 2 study is planned to initiate in patients with sickle cell disease in the second half of 2021.

ASCO Poster Presentation

Title: Phase 2 Study of MGTA-145 + Plerixafor for Rapid and Reliable Hematopoietic Stem Cell (HSC) Mobilization for Autologous Stem Cell Transplant in Multiple Myeloma (Abstract #8023)

Author: Surbhi Sidana, M.D., Assistant Professor of Medicine in the Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine
Poster Session: Hematologic Malignancies – Plasma Cell Dyscrasia
Date/Time: All e-posters are now available in the ASCO (Free ASCO Whitepaper) Annual Meeting virtual platform

These results will also be presented as an encore at the EHA (Free EHA Whitepaper) Virtual Congress, available via the conference’s virtual platform on Friday, June 11 at 3:00am EDT / 9:00am CEST.