On June 4, 2021 Sarah Cannon reported it will present its latest cancer research insights at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) Annual Meeting being held virtually June 4-8, 2021 (Press release, Sarah Cannon Research Institute, JUN 4, 2021, View Source [SID1234583598]). This year, Sarah Cannon’s drug development, molecular profiling, and clinical care expertise is featured through 119 abstracts and presentations, including data from 70 phase 1 studies. Throughout the weekend, Sarah Cannon experts will engage in 113 oral presentations, poster discussion sessions, and poster presentations as well as more than 10 invited lectures.

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"From early-phase drug development to breaking down barriers in oncology care, Sarah Cannon leaders will discuss a variety of key topics that are helping to accelerate progress in patient care," said Howard A. "Skip" Burris III, MD, FACP, FACSO, President, Clinical Operations & Chief Medical Officer, Sarah Cannon. "Our ability to match targeted therapies to the molecular drivers of tumor expressions is generating greater insights into how we can personalize medicine for every individual."

In addition to representing Sarah Cannon during the Annual Meeting, Dr. Burris currently serves as Chair of the ASCO (Free ASCO Whitepaper) Board of Directors and Conquer Cancer, the ASCO (Free ASCO Whitepaper) Foundation.

June 4 Highlights

Dee Anna Smith, Chief Executive Officer, Sarah Cannon, will present "The Empowerment of Female Leaders" in the "Dismantling Gender Disparities in the Global Oncology Workforce Together" Education Session on June 4 at 8 a.m. CDT.
Andrew Kennedy, MD, Physician-in-Chief, Radiation Oncology, Sarah Cannon; Director, Radiation Oncology Research, Sarah Cannon Research Institute, will present "Radiation Oncology Perspective" in the "Barriers to Comprehensive Multidisciplinary Head and Neck Cancer Care in a Community Oncology Practice" Education Session on June 4 at 8 a.m. CDT.
Andrew McKenzie, PhD, Director, Personalized Medicine, Sarah Cannon; Scientific Director, Genospace, will present "Integrating Molecular Insights into Multidisciplinary Planning" as part of the "Reaching More Patients: The Challenges and Opportunities of Bringing Multidisciplinary Care to Communities" Education Session on June 4 at 8 a.m. CDT.
Gerald Falchook, MD, MS, Director, Drug Development, Sarah Cannon Research Institute at HealthONE, will present "A First-In-Human Phase 1 Study of a Novel PARP7 Inhibitor RBN-2397 in Patients with Advanced Solid Tumors" in an oral presentation on June 4 from 10 a.m. – 1 p.m. CDT.
Erika Hamilton, MD, Director, Breast Cancer and Gynecologic Cancer Research, Sarah Cannon Research Institute, will present "Hunting HER2 in Solid Tumors: Margetuximab-Cmkb, Tucatinib, and Trastuzumab Deruxtecan" in the "FDA Approvals and Their Incorporation into Clinical Practice" Education Session on June 4 at 10 a.m. CDT.
Dax Kurbegov, MD, Vice President & Physician-in-Chief, Clinical Programs, Sarah Cannon, will present "Highlights of Health Services Research and Quality Improvement" in the "Health Services Research and Quality Improvement" Highlights of the Day Session on June 4 at 5 p.m. CDT.
Meredith McKean, MD, MPH, Associate Director, Melanoma and Skin Cancer Research, Sarah Cannon Research Institute, will present "Highlights of Developmental Therapeutics-Molecularly Targeted Agents and Tumor Biology" in the "Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology Highlights" Highlights of the Day Session on June 4 at 5 p.m. CDT.
Poster Discussion Highlights (Available Online June 4)

Howard A. "Skip" Burris, III, MD, will present "A First In Human Study of AO-176, a Highly Differentiated Anti-CD47 Antibody, in Patients with Advanced Solid Tumors."
Todd Bauer, MD, Senior Investigator, Drug Development, Sarah Cannon Research Institute at Tennessee Oncology, will present "Phase IB Study of The Anti-TGF-β Monoclonal Antibody NIS793 Combined with Spartalizumab, a PD-1 Inhibitor, in Patients with Advanced Solid Tumors."
Elisa Fontana, MD, PhD, Translational Oncologist & Research Fellow, Sarah Cannon Research Institute – UK, will present "Early-Onset Stage II/III Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes From Adjuvant Fluoropyrimidine and Oxaliplatin."
Erika Hamilton, MD, will present "Phase I/II Study of H3B-6545, a Novel Selective Estrogen Receptor Covalent Antagonist, in Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Advanced Breast Cancer."
Manish Patel, MD, Director, Drug Development, Sarah Cannon Research Institute at Florida Cancer Specialists, will present "BDB001, an Intravenously Administered Toll-Like Receptor 7 and 8 Agonist, in Combination with Pembrolizumab in Advanced Solid Tumors: Phase 1 Safety and Efficacy Results."
Debra Richardson, MD, FACOG, FACS, Associate Professor, Gynecologic Oncology, Stephenson Cancer Center | Sarah Cannon Research Institute, will present "A Tale of Three PARP Inhibitors."
David Spigel, MD, Chief Scientific Officer, Sarah Cannon Research Institute, will present "Five-Year Survival Outcomes with Durvalumab after Chemoradiotherapy in Unresectable Stage III NSCLC: An Update from the PACIFIC Trial."
Poster Highlights (Available Online June 4)

Gerald Falchook, MD, MS, will present "A Phase 1 Dose-Escalation Study of Intravenously Administered TAK-676, a Novel STING Agonist, Alone and in Combination with Pembrolizumab in Patients with Advanced or Metastatic Solid Tumors."
Erika Hamilton, MD, will present "LIO-1: Lucitanib + Nivolumab in Patients with Advanced Solid Tumors – Updated Phase 1b Results and Initial Experience in Ph2 Ovarian Cancer Cohort."
Maen Hussein, MD, Principal Investigator, Sarah Cannon Research Institute at Florida Cancer Specialists, will present "Platform Trial of Ezabenlimab, an Anti-PD-1 Antibody, in Patients with Previously Treated Advanced Solid Tumors: Combination with BI 836880, a VEGF/Ang2-Blocking Nanobody."
Melissa Johnson, MD, Director, Lung Cancer Research, Sarah Cannon Research Institute, will present "Phase 1 & Phase 2a, First-In-Human Study, of DRP-104, a Broad Glutamine."
Carissa Jones, PhD, Senior Program Specialist, Personalized Medicine, Sarah Cannon, will present "Impact of Immune Checkpoint Inhibitor and EGFR Tyrosine Kinase Inhibitor Sequence on Time to Treatment Failure among EGFR+ NSCLC Treated in a Community-Based Cancer Research Network."
Meredith McKean, MD, MPH, will present "Association of Combined Phase I/II Study of a Novel Bicyclic Peptide and MMAE Conjugate BT8009 in Patients with Advanced Malignancies with Nectin-4 Expression."
Manish Patel, MD, will present "A Phase 1/2 Open-Label Study of KY1044, an Anti-ICOS Antibody with Dual Mechanism of Action, as Single Agent and in Combination with Atezolizumab, in Adult Patients with Advanced Malignancies."
Emma Sturgill, PhD, Program Specialist, Personalized Medicine, Sarah Cannon, will present "Concordance of Blood and Tissue TMB from NGS Testing in Real World Settings and Their Ability to Predict Response to Immunotherapy."
Michael Tees, MD, Hematologist/Oncologist, Colorado Blood Cancer Institute, a part of Sarah Cannon Cancer Institute at Presbyterian/St. Luke’s Medical Center, will present "Safety and PK/PD of ALLO-647, an Anti-CD52 Antibody, with Fludarabine/Cyclophosphamide for Lymphodepletion in the Setting of Allogeneic CAR-T Cell Therapy."
June 7 Highlights

Gerald Falchook, MD, MS, will chair "Developmental Therapeutics—Immunotherapy Track" on June 7 from 2-5 p.m. CDT.
Judy Wang, MD, Associate Director, Drug Development, Sarah Cannon Research Institute at Florida Cancer Specialists, will present "Novel Strategies for Overcoming Resistance to Immune Checkpoint Inhibitors" as part of "Developmental Therapeutics—Immunotherapy Track" on June 7 from 2-5 p.m. CDT.
Tara Gregory, MD, Unrelated Donor Program Director; Multiple Myeloma Program Co-Director, Colorado Blood Cancer Institute, a part of Sarah Cannon Cancer Institute at Presbyterian/St. Luke’s Medical Center, will present "CD20-Directed CAR T" as part of "Developmental Therapeutics—Immunotherapy Track" on June 7 from 2-5 p.m. CDT.
June 8 Highlights

Jesus Berdeja, MD, Director, Myeloma Research, Sarah Cannon Research Institute, will present "Updated Results of a Phase 1, First-In-Human Study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D × CD3 Bispecific Antibody, in Relapsed/Refractory Multiple Myeloma" in an oral presentation on June 8 from 7-10 a.m. CDT.
Marlana Orloff, MD, Assistant Professor, Department of Medical Oncology, Sidney Kimmel Cancer Center at Jefferson Health | Sarah Cannon Research Institute, will present "Mutation Landscape and Emerging Therapies in Uveal Melanoma" in the "Beyond BRAF: Targeted Therapy for Non-BRAF Melanoma" Education Session on June 8 at 10:30 a.m. CDT.
The researchers are a part of Sarah Cannon’s global network of strategic sites, including:

Sarah Cannon Research Institute at Tennessee Oncology, Sarah Cannon Research Institute at Florida Cancer Specialists, Colorado Blood Cancer Institute, Sarah Cannon Blood Cancer Center at St. David’s South Austin Medical Center, Sarah Cannon Center for Blood Cancer at TriStar Centennial, Sarah Cannon Research Institute at HCA Midwest Health (Kansas City), Sarah Cannon Research Institute at HealthONE (Denver), Sarah Cannon Research Institute – United Kingdom, Sidney Kimmel Cancer Center at Jefferson Health, and The Stephenson Cancer Center at the University of Oklahoma.

On June 4, 2021 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing a novel class of T cell engagers, reported a pipeline update on its four clinical stage programs, including updating the interim data presented earlier at ASCO (Free ASCO Whitepaper) from the ongoing dose escalation portion of the Phase 1/2a trial for HPN424 in patients with metastatic castration resistant prostate cancer (mCRPC) (Press release, Harpoon Therapeutics, JUN 4, 2021, View Source [SID1234583615]). Harpoon has four product candidates in clinical trials that are based on its proprietary Tri-specific T cell Activating Construct (TriTAC) platform designed to recruit a patient’s own immune cells to kill tumor cells.

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"We are excited by the clinical data emerging from our four TriTAC programs that are showing tumor size reductions or stable disease, meaningful treatment duration, clinical activity, target engagement, extended half-life, and manageable safety and tolerability profiles in the heavily pretreated patient populations," stated Jerry McMahon, Ph.D., President and CEO, Harpoon Therapeutics. "As we continue to advance to higher doses in each of these programs, we look forward to the initiation of expansion cohorts this year."

"The clinical signals observed in the HPN424 trial and the unconfirmed partial response in the recently initiated HPN328 trial are very encouraging," said Natalie Sacks, M.D., Chief Medical Officer of Harpoon. "Looking across the portfolio, we are encouraged by how our novel technology is performing across multiple tumor types. We are seeing initial signs of clinical activity while effectively managing cytokine-mediated adverse events."

Dose escalation and step dosing for HPN424 Phase 1/2a clinical trial continuing.
As of May 31, 2021, the data cutoff date for the Company’s HPN424 presentation, the Company updated the ASCO (Free ASCO Whitepaper) interim data to describe newly enrolled patients and additional follow-up on existing patients already enrolled in the 300 ng/kg step dose cohort. The company has examined several step dosing regimens in this cohort and had the following observations:

Eight patients most recently enrolled in this cohort were treated with the same modified step dose regimen. Preliminary data from these patients include 3/8 (38%) with PSA declines that occur early in the course of treatment.

For the total 19 patients enrolled in this cohort, 4/19 showed PSA declines, including two patients with PSA30.
The ASCO (Free ASCO Whitepaper) poster presentation, included the following observations:

Antitumor activity includes a confirmed PR per RECIST, PSA declines and CTC reductions.
Fifteen of 74 (20%) pts with >1 post-baseline value had PSA decreases from baseline ranging from -2% to -76%, including 4 pts with PSA50 response and 2 pts with PSA30 response
Treatment duration > 24 weeks observed in 15 of 74 (20%) pts, including 8 of 17 (47%) chemo-naïve patients
Reduction in CTCs was seen in 36 of 64 (56%) patients with available baseline and on-treatment CTC counts
CRS has been transient and manageable with 4% of patients experiencing Grade 3 CRS
CRS and transaminitis events observed most often in Cycle 1, with diminished frequency and severity in subsequent cycles
Introduction of step dose regimens has allowed for the administration of higher target doses, currently at 300ng/kg
HPN536 (mesothelin TriTAC) Phase 1/2a clinical trial continues dose escalation. Dosing has occurred across 10 fixed-dose cohorts of 6 to 560ng/kg and three step dose cohort up to 1200ng/kg, with total enrollment of 60 patients. Tumor types treated include late-stage ovarian (47%), pancreatic (40%) and peritoneal and pleural mesothelioma (13%) cancers. Pharmacokinetic analysis shows median half-life of more than 70 hours for HPN536. Among the relapsed/refractory ovarian cancer patients with at least one post-baseline scan, 11 of 20 (55%) patients showed stability of target lesions, including three patients with target lesion shrinkage. In addition, five of 27 (19%) ovarian cancer patients had a duration of treatment of greater than 24 weeks. As of May 31, 2021, MTD has not been reached. The Company expects to present interim data at a medical conference in 2021.

Dose escalation for HPN217 (BCMA TriTAC) Phase 1/2 clinical trial making good progress. Relapsed/refractory multiple myeloma patients (N=20) have been treated across eight fixed dose cohorts of 5 to 2150 µg weekly, reflecting rapid dose expansion since the trial began. HPN217 has been well tolerated, and no DLTs have been observed as of the May 10, 2021 cutoff date. Pharmacokinetic analysis shows half-life extension to support at least once weekly dosing. A presentation of interim data is anticipated as well as initiation of a dose expansion cohort in the second half of 2021.

Dose escalation for HPN328 (DLL3 TriTAC) Phase 1/2 clinical trial initiated in late 2020 and has shown rapid progress. The first single patient cohort began with a flat dose of 15µg of HPN328 administered once weekly by intravenous infusion and has proceeded to the fourth cohort at a dose of 405µg. Eligible patients include small cell lung cancer patients who have relapsed after platinum chemotherapy and patients with other tumors associated with DLL3 expression. An unconfirmed partial response has been observed for one patient with small cell lung cancer from the 45µg dose cohort. Presentation of initial interim data is planned for the second half of 2021.

IND-enabling studies for HPN601 (EpCAM ProTriTAC) are progressing as planned. HPN601 is a conditionally active T cell engager based on the ProTriTAC platform. EpCAM is expressed in a broad range of solid tumors, including gastrointestinal cancers, potentially enabling HPN601 to address multiple indications with high unmet medical need.

Conference Call and Webcast Today

Harpoon’s management will host a webcast and conference call at 4 p.m. ET / 1 p.m. PT on Friday, June 4, 2021 to review the data presented at ASCO (Free ASCO Whitepaper) and provide an update on its other pipeline programs. The live call may be accessed by dialing 866-951-6894 for domestic callers or 409-216-0624 for international callers and using conference ID # 2657278.

A live webcast of the call will be available from the Events and Presentations section of the company’s website at View Source and will be archived there shortly after the live event.

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 Heat Biologics, Inc. (Nasdaq: HTBX), a clinical-stage biopharmaceutical company focused on developing first-in-class therapies to modulate the immune system, reported that Dr. Roger B. Cohen, MD, Professor of Medicine at the University of Pennsylvania Perelman School of Medicine, presented an overview of the latest HS-110 data at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting which is being held from June 4-8, 2021 (Press release, Heat Biologics, JUN 4, 2021, View Source [SID1234583533]). This poster presentation can be viewed on Heat Biologics’ website at: View Source The ASCO (Free ASCO Whitepaper) Annual Meeting is the world’s largest oncology conference showcasing the latest advancements in cancer research.

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

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HS-110, in combination with a checkpoint inhibitor (CPI), is a potentially transformational agent to improve survival benefit for patients with non-small cell lung cancer (NSCLC). This is a first-in-class, allogeneic, off-the shelf cell-based therapy developed by Heat leveraging its proprietary gp96 platform. At this year’s ASCO (Free ASCO Whitepaper) meeting, the Company is pleased to report the latest data of HS-110 in combination with OPDIVO (nivolumab) in two distinct treatment settings in a total of 115 previously treated patients with NSCLC:

Median overall survival (mOS) of 24.6 months was observed in previously treated, CPI naïve patients with advanced NSCLC (Cohort A, n=47). This data compares favorably with published data of Checkmate 057, which reported a mOS of 12.2 months in patients who received nivolumab as single agent in a similar treatment setting.
mOS of 11.9 months was reported in NSCLC patients who were previously treated with CPI and whose disease had subsequently progressed (Cohort B, n=68). Published data from other studies stated median OS of 6.8 to 9.0 months for NSCLC patients treated with chemotherapies after CPI progression.
Multiple subset analyses including injection-site reaction (ISR) and tumor PD-L1 expression were performed.
Significantly longer mOS was observed in patients with ISR compared with those without such a reaction for both Cohorts A and B.
Extended survival benefit was observed in PD-L1 positive patients in Cohort A.
A trend of improved overall survival was observed in patients with low blood tumor mutation burden in Cohort B.
Dr. Roger B. Cohen, Professor of Medicine at the University of Pennsylvania Perelman School of Medicine, commented, "HS-110 is a promising agent for treatment of incurable NSCLC. The latest data presented support further clinical evaluation in combination with first line regimens that include a CPI as well as addressing high unmet medical needs for CPI progressors."

Jeff Wolf, Chief Executive Officer of Heat, commented, "This data further reinforces the potential utility of HS-110 in combination with a CPI for multiple treatment settings of NSCLC. The growing body of clinical data demonstrates that HS-110 in combination with a CPI is well tolerated and has the potential to enhance survival benefit when given with a CPI. Our latest results, consistent with previously reported data, provide a strong foundation for the Company to discuss possible Phase 3 registration trial designs with the FDA and potential partners."

About HS-110
HS-110 is a first-in-class, off-the-shelf, allogeneic cell therapy designed to utilize gp96 for immune activation against multiple tumor testis antigens. Phase 2 trial of HS-110 in combination with Bristol Myers Squibb’s OPDIVO (nivolumab) has completed enrollment in patients with incurable or metastatic NSCLC. OPDIVO is a programmed death-1 immune checkpoint inhibitor. HS-110 has broad potential for providing multiple treatment options to NSCLC patients in combination with a PD-1 inhibitor. Positive interim survival data has been demonstrated in two distinct treatment settings in previously treated NSCLC patients who have not been treated with CPI as well as patients who have progressed during or after previous treatment with a CPI. Combination of HS-110 and PD-(L)1 therapies may confer additional survival benefit.

On June 4, 2021 Shanghai Junshi Biosciences Co., Ltd ("Junshi Biosciences", HKEX: 1877; SSE: 688180) and Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) reported that the companies will host a virtual investor event on Monday, June 7, 2021 at 6 p.m. Eastern Time to discuss toripalimab clinical data from the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Coherus Biosciences, JUN 4, 2021, View Source [SID1234583550]).

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!

Key highlights will include a discussion of toripalimab discovery and early development, a review of data presented at ASCO (Free ASCO Whitepaper), including the results of the JUPITER-02 clinical trial evaluating toripalimab for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma, and an overview of the broad toripalimab clinical development program and strategy for marketing authorization. Event participants will include the following:

Dr. RuiHua Xu, President and Professor at Sun Yat-sen University Cancer Center
Dr. Sheng Yao, Senior Vice President of Junshi Biosciences
Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences
Denny Lanfear, Chief Executive Officer of Coherus

Please dial-in/login 15 minutes early to ensure a timely connection to the call. An archived edition of the event will be available later that day.

A slide presentation will be posted prior to the event to the Investors section of the Coherus website.