On May 26, 2022 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported financial results for the quarter ended March 31, 2022 (Press release, Can-Fite BioPharma, MAY 26, 2022, View Source [SID1234615073]).

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"Can-Fite is financially well positioned to conduct all our clinical development programs over the next year, and we continue to evaluate potential new distribution partnerships which may provide additional non-dilutive funding."

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Corporate and Clinical Development Highlights Include:

Fortified Balance Sheet – On March 31, 2022, Can-Fite had approximately $16.5 million in cash, cash equivalents, and short-term deposits.

Phase III Psoriasis Study Data Expected Q2 2022 – Topline results are expected in Q2 2022 in Can-Fite’s Phase III Comfort psoriasis study for both its 16 week primary endpoint and 32 week secondary endpoint. The study is designed to establish Piclidenoson’s superiority compared to placebo at 16 weeks and non-inferiority compared to Apremilast (Otezla) at 32 weeks. During the first quarter, a preclinical study showed Piclidenoson destroyed pathological skin cells, offering further evidence of potential efficacy in psoriasis.

Developing Topical Psoriasis Treatment – In a preclinical model, daily treatment with topical Piclidenoson significantly inhibited psoriasis as measured by the psoriasis area severity index (PASI) calculated based on observation of erythema, thickness, scaling, and a score of skin lesions. The topical treatment may serve as a complementary product to oral Piclidenoson.

Commenced Enrollment in Phase IIb NASH Study – In January, Can-Fite enrolled the first patient in its Phase IIb multicenter, randomized, double-blind, placebo-controlled study in 140 subjects with biopsy-confirmed NASH. The primary objective of the trial is to evaluate the efficacy of Namodenoson as compared to placebo as determined by a histological endpoint. In a prior Phase IIa study, Namodenoson met its primary endpoint by reducing liver fat, inhibiting fibrosis, and demonstrating an anti-inflammatory effect.

Granted U.S. Patent for Liver Fibrosis and Israeli Patent for NASH – The U.S. Patent and Trademark Office granted Can-Fite a patent for its invention titled "Method for Treating Fibrotic Liver Tissue Using CL-IB MECA", a broad patent that addresses markets for the treatment of all advanced liver fibrosis indications. The patent opens an opportunity for much broader market needs which entail all clinical conditions with advanced liver fibrosis including autoimmune hepatitis, primary biliary cirrhosis (PBC), nonalcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD) among others. The Israel Patent Office granted Can-Fite a patent titled "An A3 Adenosine Receptor Ligand For Use In Treating Ectopic Fat Accumulation" which has been issued in approximately 40 other countries.

Opened Enrollment in Pivotal Phase III Liver Cancer Study – Can-Fite’s pivotal Phase III liver cancer study for Namodenoson opened for enrollment of approximately 450 patients diagnosed with hepatocellular carcinoma (HCC) and underlying Child Pugh B7 (CPB7) who have not responded to other approved therapies. An interim analysis will be conducted after 50% of patients are enrolled and treated. The primary endpoint is overall survival. Can-Fite has received Orphan Drug Designation in both the U.S. and Europe and has received the U.S. FDA’s Fast Track Status.

Presented Data on Cannabinoids in the Treatment of Liver Cancer at CannX – In March, Can-Fite delivered a presentation titled "Inhibition of Hepatocellular Carcinoma Growth and Liver Fibrosis by Nanomolar Cannabinoids Concentrations" at the CannX Medical Cannabis Conference in Tel Aviv. The findings were also published in the peer-reviewed scientific journal Medical Cannabis and Cannabinoids highlighting the ability of CBD-rich T3/C15 in nanomolar concentrations to inhibit the growth of hepatocellular carcinoma and liver stellate cells via A3AR activation and deregulation of the Wnt/β-catenin pathway.

"We look forward to announcing Phase III psoriasis results before the end of the second quarter as we enroll patients in our other advanced stage clinical trials for NASH and liver cancer," stated Can-Fite CEO Dr. Pnina Fishman. "Can-Fite is financially well positioned to conduct all our clinical development programs over the next year, and we continue to evaluate potential new distribution partnerships which may provide additional non-dilutive funding."

Financial Results

Revenues for the three months ended March 31, 2022 were $0.20 million, an increase of $0.05 million, or 38.5%, compared to $0.15 million for the three months ended March 31, 2021. The increase in revenues was mainly due to the recognition of a higher portion of advance payments received under a distribution agreement with Ewopharma than the advance payment received at the end of the first quarter of 2021.

Research and development expenses for the three months ended March 31, 2022 were $1.82 million, an increase of $0.52 million, or 39.8%, compared to $1.30 million for the three months ended March 31, 2021. Research and development expenses for the first quarter of 2022 comprised primarily of expenses associated with an ongoing Phase III study of Piclidenoson for the treatment of psoriasis and two studies for Namodenoson, a Phase III study in the treatment of liver cancer and a Phase IIb study for NASH. The increase is primarily due to costs incurred in the first quarter of 2022 associated with the two new studies for Namodenoson.

General and administrative expenses for the three months ended March 31, 2022 were $0.75 million a decrease of $0.26 million, or 25.8%, compared to $1.01 million for the three months ended March 31, 2021. The decrease is primarily due to the decrease in professional services for public relations and investor relations. We expect that general and administrative expenses will remain at the same level through 2022.

Financial expenses, net for the three months ended March 31, 2022 were $0.06 million compared to finance income, net of $0.29 million for the three months ended March 31, 2021. The decrease in financial income, net was mainly due to revaluation of our short-term investment which in 2021 was recorded as income and in 2022 was recorded as expense.

Net loss for the three months ended March 31, 2022 was $2.43 million compared with a net loss of $1.87 million for the three months ended March 31, 2021. The increase in net loss for the three months ended March 31, 2022 was primarily attributable to an increase in research and development expenses which was partly offset by a decrease in general and administrative expenses and a decrease in finance income, net.

As of March 31, 2022, Can-Fite had cash and cash equivalents and short term deposits of $16.5 million as compared to $18.9 million at December 31, 2021. The decrease in cash during the three months ended March 31, 2022 is due to the ongoing operation of the Company.

The Company’s consolidated financial results for the three months ended March 31, 2022 are presented in accordance with US GAAP Reporting Standards.

On May 26, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported promising initial data from a Phase 1/2 study evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and subgroup analyses and molecular classification data from the SIENDO study evaluating selinexor in endometrial cancer (Press release, Karyopharm, MAY 26, 2022, View Source [SID1234615090]). These data, and four additional abstracts, will be presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO 2022), being held in Chicago from June 3-7, 2022.

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Results from Phase 1/2 Study Evaluating Selinexor in Combination with Ruxolitinib in Patients with Treatment-Naïve Myelofibrosis
The initial data to be presented at ASCO (Free ASCO Whitepaper) 2022 were based on the Phase 1 portion of the Phase 1/2 study evaluating the safety and preliminary efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis. As of May 1, 2022, 15 patients had been dosed with one of two dose levels of selinexor, 40 mg (n=3) and 60 mg (n=12), in combination with ruxolitinib 15/20 mg BID.

Seventy-five percent of evaluable patients (6 out of 8) demonstrated ≥35% reduction in spleen volume (SVR35) at week 12. Five out of 10 transfusion independent patients who had at least eight weeks of treatment maintained stable hemoglobin (± 2g/dL) or improved hemoglobin level (>2g/dL increase) at last follow up. In addition, all of the evaluable 7 patients, who had been at least 12 weeks on treatment and had complete data, experienced rapid reductions in their symptom scores with 3 of 7 patients having ≥50% reduction (TSS50) at week 12.

There were two patients who discontinued therapy in the trial: One patient discontinued after 5 months of therapy due to unrelated AEs (dizziness, atrial fibrillation, and pulmonary hypertension) and another patient discontinued after 8 weeks of therapy due to progression to AML.

The combination of selinexor and ruxolitinib was generally well-tolerated and manageable. No dose-limiting toxicities were reported at either dose level of selinexor, and the most common adverse event (AE) was nausea (40%), the majority of which were grade 1/2. Both the 40 mg and 60 mg dose levels were generally well tolerated, with the most common reported Grade 3-4 treatment-emergent AEs being thrombocytopenia (27%), anemia (20%), neutropenia (20%) and atrial fibrillation (20%). Hematologic adverse events were reversible with dose interruptions and reductions.

The trial is currently enrolling patients in the Phase 1b dose expansion part of the study.

"Despite tremendous improvements in the lives of patients with myelofibrosis with the introduction of the JAK inhibitors, there remains a significant unmet need. We are excited to develop a novel combination that may further improve outcomes for these patients," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "Following the promising initial results of selinexor in relapsed and refractory myelofibrosis, we are very excited with these preliminary data in treatment-naïve myelofibrosis patients in combination with ruxolitinib, with encouraging results seen across multiple measures including spleen volume reductions, improvements in symptom scores and management of anemia. We look forward to sharing these promising initial data with the broader medical and scientific community at ASCO (Free ASCO Whitepaper) 2022."

SIENDO Study Subgroup Analysis
A preliminary analysis of exploratory subgroups of the SIENDO study assessed four distinct molecular subtypes in endometrial cancer using The Cancer Genome Atlas (TCGA), one of the accepted gynecologic oncology algorithms that is used to calculate prognostic risk scores. This analysis indicated that patients with p53 wild-type endometrial cancer treated with selinexor showed a median progression-free survival of 13.7 months compared to 3.7 months for patients on placebo.

"These data suggest that selinexor may provide meaningful benefit to patients with p53 wild-type endometrial cancer and reinforce the need to further evaluate selinexor’s potential in a registration-enabling Phase 3 study, that we are planning to initiate in the second half of this year," added Dr. Rangwala.

Details for the ASCO (Free ASCO Whitepaper) 2022 selinexor presentations are as follows:
Oral Presentation

Title: Randomized phase III study of maintenance selinexor versus placebo in endometrial cancer (ENGOT – EN5/GOG-3055/SIENDO): Impact of subgroup analysis and molecular classification
Presenter: Vicky Makker, Memorial Sloan Kettering Cancer Center
Abstract #: 5511
Date and time: Tuesday, June 7, 2022, 9:48 a.m. – 10:00 a.m. EDT
Session: Clinical Science Symposium/Molecular-Based Treatment for Endometrial Cancer

Poster Presentations

Title: A phase 1, open-label, dose-escalation study of selinexor plus ruxolitinib in patients with treatment-naïve myelofibrosis
Presenter: Haris Ali, City of Hope
Abstract #: 7060
Date and time: Saturday, June 4, 2022, 9:00 a.m. – 12:00 p.m. EDT
Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Title: Phase Ib trial of selinexor (SEL) in combination with nivolumab (NIVO) alone or nivolumab plus ipilimumab (NIVO+IPI) in patients (pts) with advanced malignancies: The renal cell carcinoma (RCC) experience.
Presenter: Omar Alhalabi, The University of Texas MD Anderson Cancer Center
Abstract #: 4551
Date and time: Saturday, June 4, 2022, 2:15 p.m. – 5:15 p.m. EDT
Session: Genitourinary Cancer–Kidney and Bladder

Title: Phase 1b study of weekly split-dose selinexor in soft tissue sarcoma (STS)
Presenter: Abdulazeez Salawu, University Health Network
Abstract #: 11563
Date and time: Sunday, June 5, 2022, 9:00 a.m. – 12:00 p.m. EDT
Session: Sarcoma

Title: Digital monitoring and assessments in patients with glioblastoma
Presenter: Yasaman Damestani, Karyopharm Therapeutics, Inc.
Abstract #: 2045
Date and time: Sunday, June 5, 2022, 9:00 a.m. – 12:00 p.m. EDT
Session: Central Nervous System Tumors

Title: Phase Ib study of selinexor and eribulin combination in advanced solid tumors and triple-negative breast cancer
Presenter: Blessie Elizabeth Nelson, University of Texas MD Anderson Cancer Center
Abstract #: 3108
Date and time: Sunday, June 5, 2022, 9:00 a.m. – 12:00 p.m. EDT
Session: Developmental Therapeutics–Molecularly Targeted Agents and Tumor Biology

About the SIENDO Study
The Phase 3 SIENDO study (ENGOT-EN5/GOG-3055) is a multicenter, blinded, placebo-controlled, randomized study evaluating the efficacy and safety of selinexor as a maintenance therapy following chemotherapy in patients with advanced or recurrent endometrial cancer. The study enrolled 263 patients with primary stage IV or recurrent disease who had a partial or complete response after at least 12 weeks of standard taxane-platinum combination chemotherapy. Patients were randomized 2:1 to receive either maintenance therapy of 80mg of selinexor taken once weekly, or placebo, until disease progression. The primary endpoint of the study was statistically significant improvement of progression-free survival compared to placebo. The goal of the study was to demonstrate a hazard ratio of 0.6 or better. In partnership with Karyopharm, the study was initiated by the European Network for Gynaecological Oncological Trial (ENGOT) group. In the U.S., the collaboration includes the GOG Foundation, Inc. (GOG-F).

About XPOVIO (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea, Singapore and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including multiple myeloma, endometrial cancer and myelofibrosis. For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

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

XPOVIO (selinexor) is a prescription medicine approved:

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

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

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions were infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.

On May 26, 2022 Veracyte, Inc. (Nasdaq: VCYT) reported that new data from a large, population-based study reinforce the clinical utility of the Decipher Prostate genomic classifier (Press release, Veracyte, MAY 26, 2022, View Source [SID1234615106]). The findings, which will be shared for the first time at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, suggest that the Decipher Prostate tests are helping to guide prostate cancer treatment decisions and improve patient care.

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"This is the first study linking patient data from SEER, the most commonly used cancer database in the United States, and the Decipher Prostate genomic classifier, to explore the association between Decipher Prostate test results and prostate cancer treatment decisions," said Elai Davicioni, Ph.D., Veracyte’s medical director for urology and an author on the study. "The resulting data are exciting, because they demonstrate that population-based prostate cancer treatment patterns are independently associated with Decipher classifier scores."

Researchers identified 10,528 patients with a primary prostate cancer diagnosis from 2010 to 2018 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database who had undergone testing with either Decipher Prostate Biopsy (n=5,015) or Decipher Prostate RP (n=5,513) between 2014 and 2020. They then evaluated the association between these patients’ Decipher scores (range 0-1) and risk groups (low, intermediate and high), and the use of active surveillance and watchful waiting (AS/WW) as well as adverse pathology at the time of radical prostatectomy (RP).

Results show that use of AS/WW was highest among those men with low risk Decipher Prostate Biopsy results (41%), as compared to men who had intermediate (32%) or high risk (17%) Decipher scores. Conversely, RP usage increased based on individuals’ Decipher test risk group (19% of low, 25% of intermediate, and 34% of high risk). Researchers observed a similar association and trend by Decipher risk group in the use of radiation therapy (13% of low, 19% of intermediate, and 29% of high Decipher risk).

"These findings provide a powerful demonstration that the Decipher Prostate genomic classifiers are giving physicians and patients valuable information to help them make important and often challenging treatment decisions. In other words, the test is positively impacting patient care, as intended," said Dr. Davicioni. "We are thrilled to be collaborating with the National Cancer Institute’s SEER program and academic researchers from leading comprehensive cancer centers and believe that these data will substantially enrich SEER’s prostate cancer registry and provide a valuable resource for oncology researchers."

About Decipher Prostate

Decipher Prostate is a 22-gene, microarray-based genomic test intended to help inform treatment decisions for men with localized prostate cancer at initial diagnosis (Decipher Prostate Biopsy) and after surgical removal of the prostate (Decipher Prostate RP). The test reports the Decipher Score, which prognosticates a patient’s risk of metastasis within five years and provides risk estimates of prostate cancer-specific outcomes. Decipher Prostate can help guide physicians to better select the appropriate therapy for a specific patient, which in turn can result in improved patient outcomes.

On May 26, 2022 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported initial dose-escalation data from the Phase 1 study evaluating XmAb104, a PD-1 x ICOS bispecific antibody, in patients with advanced solid tumors (DUET-3) (Press release, Xencor, MAY 26, 2022, View Source [SID1234615122]). These results will be presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), during the poster session "Developmental Therapeutics—Immunotherapy" on Sunday, June 5, 2022, from 8:00 a.m. to 11 a.m. CDT in Hall A at McCormick Place in Chicago.

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DUET-3 is an ongoing Phase 1 study of XmAb104 to assess the candidate’s safety and tolerability profile in patients with advanced solid tumors and to determine the maximum tolerated dose (MTD). The expansion portion of the study is currently enrolling patients with colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), non-squamous non-small cell lung cancer (NSCLC), sarcoma, melanoma and clear-cell renal cell carcinoma (RCC) and is randomizing patients 1:1 to receive 10 mg/kg intravenous XmAb104 every two weeks as monotherapy or in combination with ipilimumab.

"XmAb104 is engineered to selectively engage T cells that express both PD-1 and ICOS, important regulators of T cell activity, and we have observed biomarker activity consistent with engagement of both receptors. XmAb104 has been well tolerated and is exhibiting a distinct safety profile compared to other clinical ICOS programs, which, along with early anti-tumor activity in patients, supports its evaluation in expansion cohorts," said Allen Yang, M.D., Ph.D., senior vice president and chief medical officer at Xencor. "The ongoing expansion portion of the study is testing XmAb104, with or without the anti-CTLA-4 antibody ipilimumab, as CTLA-4 blockade has been found to increase the frequency of ICOS-expressing T cells in multiple solid tumor types."

Additionally, a trial-in-progress poster, "A phase 2, multicenter, parallel-group, open-label study of vudalimab (XmAb20717), a PD-1 x CTLA-4 bispecific antibody, alone or in combination with chemotherapy or targeted therapy in patients with molecularly defined subtypes of metastatic castration-resistant prostate cancer," will be presented during the session "Genitourinary Cancer—Prostate, Testicular, and Penile" on Monday, June 6, 2022, from 1:15 p.m. to 4:15 p.m. CDT in Hall A.

Posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com, at the time of the formal presentations at ASCO (Free ASCO Whitepaper).

Key Highlights from DUET-3 (Abstract #2604)

At the data cut off on April 15, 2022, 62 patients had been treated in nine dose-escalation cohorts escalating from 0.002 to 15 mg/kg of XmAb104 administered every other week in four-week cycles. Patients were a median age of 63 years and had a median of three prior systemic therapies. 62.9% of patients had received at least one prior checkpoint therapy, and 91.9% of patients had Stage IV disease.

Patients presented with the following primary tumor types: CRC (n=14), pancreatic adenocarcinoma (n=8), soft tissue sarcoma (n=8), melanoma (n=6), HNSCC (n=5), RCC (n=4), endometrial cancer (n=2), NSCLC (n=2) and other solid tumor types (n=8). Of the patients with CRC, eight were microsatellite stable (MSS), three were microsatellite instable (MSI) and three were not defined. Most patients had tumors generally not considered to be sensitive to checkpoint inhibition.

Safety and Tolerability

Safety was evaluated in all 62 patients. XmAb104 was well tolerated through the highest tested dose cohort, and treatment-related adverse events (TRAE) were mostly mild. The most common TRAEs (>5 patients) were decreased appetite (9.7%), diarrhea (9.7%), fatigue (9.7%) and maculopapular rash (8.1%). Immune-related adverse events were reported for a limited number of patients, were predominantly Grade 1 or 2, and showed no relationship to dose level. Two patients (3.2%) experienced serious TRAEs, including a Grade 3 hyperbilirubinemia and a Grade 4 asymptomatic lipase increase; both events resolved with prednisone. Four patients (6.5%) discontinued from the study due to an adverse event.

No dose-limiting toxicities were observed, and the MTD was not reached. The recommended dose for continued study, based on feasibility of administration at higher dose levels and a review of safety data with investigators, was determined to be 10 mg/kg.

Clinical Activity Highlights

The efficacy analysis included 51 evaluable patients who received any amount of XmAb104 and had at least one post-baseline assessment by RECIST 1.1. At the data cut off, two confirmed partial responses (PR), one unconfirmed PR, and stable disease have been observed:

A patient with undifferentiated pleomorphic sarcoma, who was immunotherapy naïve, presented with two target lesions in the lung and a subpleural lingular nodule. The patient was enrolled into the 0.2 mg/kg cohort and dose escalated to 0.6 mg/kg. The nodule completely resolved, and a single non-target lesion remained in the lung. The confirmed partial response continued at the time of the data cut (28 months).
A patient with clear cell RCC, who had previously received treatment with pembrolizumab/axitinib, presented with two target lesions in the ribs, one target lesion in a lymph node, and a non-target lesion in bone. The patient was treated at the 10 mg/kg dose. A partial response was observed at the end of Cycle 2, and the patient remained in response at the time of the data cut (8 months).
A patient with HNSCC, who had recently received treatment with pembrolizumab, was enrolled into the 1.8 mg/kg dose cohort. Prior therapies also included neo-adjuvant nivolumab, cisplatin, nivolumab and a GAL-3 inhibitor, and the patient experienced disease progression on all prior therapies. Two target lesions in the lung were identified, and the patient experienced a partial response at the end of Cycle 2.
Two patients with CRC have experienced durable stable disease for over 20 months, both ongoing at the time of data cut. A patient with microsatellite instability high (MSI-H)-CRC was treated at an initial dose of 1.8 mg/kg and dose escalated to 10 mg/kg. Laboratory results indicated a decrease in the tumor marker CEA over time. A second patient, with MSI-H CRC, was treated at the 10 mg/kg dose, and at the time of the data cut, continued to experience stable disease in Cycle 22.
Pharmacokinetics/Pharmacokinetics Assessments

Data from assessments of pharmacokinetics (PK) and pharmacodynamics (PD) will not be shown in the poster presentation. The PK analysis indicated a linear and dose-proportional profile. Biomarker analyses indicated complete receptor saturation on peripheral T cells beginning at the 0.6 mg/kg dose level.

About XmAb104

XmAb104 is an investigational XmAb bispecific antibody designed to promote tumor-selective T-cell activation by simultaneously targeting immune checkpoint receptor PD-1 and the immune co-stimulatory receptor ICOS. Xencor’s approach to dual checkpoint inhibition and co-stimulation reduces the need for multiple antibodies and allows for more selective targeting of T cells with high target expression, which may potentially improve the therapeutic index of combination immunotherapies. In preclinical studies, dual blockade of PD-1 and ICOS with XmAb104 significantly enhanced T cell proliferation and activation, and anti-tumor activity in vivo. XmAb104 is currently being evaluated, as a monotherapy and in combination with ipilimumab, in the expansion portion of a Phase 1 clinical study for the treatment of patients with advanced solid tumors.

On May 26, 2022 Delfi Diagnostics, a pioneering developer of a new class of high-performance, affordable liquid biopsy tests for early cancer detection, reported that it will present updates at the 2022 annual meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago June 3-7 describing multiple applications for its next-generation liquid biopsy platform (Press release, Delfi Diagnostics, MAY 26, 2022, View Source [SID1234615138]).

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"Delfi has made incredible progress on our screening program over the past year. Additionally, we have identified several new potential applications for our technology that we are continuing to explore," said Victor Velculescu, MD, PhD, Delfi’s founder and CEO. "We are excited to share these updates with ASCO (Free ASCO Whitepaper)’s members as we pursue multiple applications on the Delfi platform."

Delfi will present a trial-in-progress update on DELFI-L101, a prospective, case-control study to train and test classifiers for lung cancer detection. Additionally, it will present data showing that Delfi’s Tumor Fraction score, DELFI-TFTM, strongly correlates with mutant allele frequency and could serve as a useful tool to monitor tumor burden in patients with advanced cancer.