On September 17, 2021 BeiGene (NASDAQ: BGNE; HKEX: 06160) reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending approval of BRUKINSA (zanubrutinib) for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy or first-line treatment for patients unsuitable for chemo-immunotherapy (Press release, BeiGene, SEP 17, 2021, View Source [SID1234587906]).

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"The ASPEN trial demonstrated that BRUKINSA provided deep and durable responses and offered substantial improvements in safety and tolerability over standard therapy. Patients in Europe with WM may soon have a new treatment option that can offer improved outcomes."

"Bruton’s tyrosine kinase (BTK) inhibitors have emerged as a promising treatment for WM, yet treatment discontinuation due to lack of response or side effects remains a concern," said Prof. Christian Buske, Medical Director at the University Hospital Ulm, Germany, and a trial investigator of the ASPEN study. "The ASPEN trial demonstrated that BRUKINSA provided deep and durable responses and offered substantial improvements in safety and tolerability over standard therapy. Patients in Europe with WM may soon have a new treatment option that can offer improved outcomes."

The positive CHMP opinion is based on results from the randomized, Phase 3 ASPEN clinical trial, evaluating BRUKINSA compared to ibrutinib in patients with relapsed or refractory (R/R) or treatment-naïve (TN) WM who are unsuitable for chemo-immunotherapy. Based on the modified Sixth International Workshop on Waldenström’s Macroglobulinemia (IWWM-6) response criteria (Treon 2015), the combined complete response (CR) +VGPR rate in the overall intention-to-treat (ITT) population was 28.4% with BRUKINSA (95% CI: 20, 38), compared to 19.2% with ibrutinib (95% CI: 12, 28). While this difference was not statistically significant, BRUKINSA did achieve numerically higher VGPR rates and trends towards increased response quality.1

BRUKINSA demonstrated a more favorable safety profile compared to ibrutinib with lower frequency of certain adverse events, including atrial fibrillation or flutter (2.0% vs. 15.3%) minor bleeding (48.5% vs 59.2%) and major hemorrhage (5.9% vs 9.2%).1 Of the 101 patients with WM treated with BRUKINSA, four percent of patients discontinued due to adverse events, and adverse events leading to dose reduction occurred in 14% of patients.

"The positive CHMP opinion reflects BRUKINSA’s potential role in the WM therapeutic landscape as a selective inhibitor designed to deliver sustained and continuous inhibition of BTK, offering patients the potential for reduced frequency of certain cardiovascular events like atrial fibrillation compared to ibrutinib, and underscores our bold approach to R&D," said Jane Huang, M.D., Chief Medical Officer, Hematology, at BeiGene. "We are committed to advancing the global registration of BRUKINSA and, if approved, believe it will become the preferred BTK inhibitor for patients with WM."

"We have a strong team in Europe who are excited for the opportunity to further work with the many investigators who have participated in BRUKINSA trials conducted in Europe to-date. Looking to the future, we have built a team in Europe and they are poised to help patients access BRUKINSA following its expected approval," said Gerwin Winter, Senior Vice President, Head of Commercial, Europe, at BeiGene. "We look forward to continuing our work with the European health authorities to bring BRUKINSA to patients living with this rare, incurable blood cancer."

Following the CHMP positive opinion, the European Commission will consider BeiGene’s marketing application, with a final decision expected within 67 days of receipt of the CHMP opinion. The decision will be applicable to all 27 member states of the EU plus Iceland and Norway.

About Waldenström’s Macroglobulinemia

WM is a rare lymphoma representing approximately one percent of all non-Hodgkin’s lymphomas and typically progresses slowly after diagnosis.2 The disease usually affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen may be involved.3 Throughout Europe, the estimated incidence rate of WM is approximately seven for every one million men and four for every one million women.4

About the ASPEN trial

The Phase 3 randomized, open-label, multicenter ASPEN clinical trial (NCT03053440) evaluated zanubrutinib versus ibrutinib in people with relapsed or refractory (R/R) or treatment-naïve (TN) WM. The primary objective was to establish superiority of zanubrutinib compared to ibrutinib as demonstrated by the proportion of people achieving complete response (CR) or very good partial response (VGPR). Secondary endpoints included major response rate, duration of response and progression-free survival, and safety, measured by incidence, timing and severity of treatment-emergent adverse events. The pre-specified analysis populations for the trial included the overall population (n=201) and R/R patients (n=164). Exploratory endpoints included quality of life measures.

The study includes two cohorts, a randomized cohort (cohort 1) consisting of 201 patients with a MYD88 mutation (MYD88MUT) and a non-randomized cohort (cohort 2) in which 28 patients with MYD88 wild-type (MYD88WT) received zanubrutinib because they have historically responded poorly to ibrutinib therapy.

The randomized cohort 1 enrolled 102 patients (including 83 relapsed or refractory (R/R) patients and 19 TN (patients) in the zanubrutinib arm and 99 patients (including 81 R/R patients and 18 TN patients) in the ibrutinib arm. Patients in the zanubrutinib arm were assigned to receive zanubrutinib 160 mg twice daily (BID) and patients in the ibrutinib arm received 420 mg of ibrutinib once daily (QD).

Results of cohort 2 were previously presented at the 24th Congress of European Hematology Association (EHA) (Free EHA Whitepaper) and showed an overall response rate (ORR) of 80.8%, a major response rate (MRR; partial response or better) of 53.8% and a VGPR rate of 23.1%.

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is approved in the following indications and regions:

For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;
For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021);
For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021);
Registered and reimbursed for the treatment of MCL in patients who have received at least one prior therapy (Israel, April 2021);
For the treatment of adult patients with WM who have received at least one prior therapy (China, June 2021)**;
For the treatment of MCL in adult patients who have received at least one prior therapy (Canada, July 2021);
For the treatment of MCL in adult patients who have received at least one prior therapy (Chile, July 2021);
For the treatment of adult patients with MCL who have received at least one previous therapy (Brazil, August 2021);
For the treatment of adult patients with WM (United States, August 2021); and
For the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (United States, September 2021)*.
To date, more than 30 marketing authorization applications in multiple indications have been submitted in the United States, China, the European Union, and more than 20 other countries or regions.

* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 27% of patients, most commonly pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 8% of patients. Other second primary malignancies included malignant solid tumors (4.0%), melanoma (1.7%) and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter were reported in 3.2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse reactions

The most common adverse reactions, including laboratory abnormalities, in ≥ 30% of patients who received BRUKINSA (N = 847) included decreased neutrophil count (54%), upper respiratory tract infection (47%), decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%) and musculoskeletal pain (30%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

On September 17, 2021 Tachyon Therapeutics, Inc. ("Tachyon" or "the Company"), a research and development biotechnology company, reported an abstract presentation of the Company’s lead product candidate, TACH101, at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) ("ESMO") Annual Meeting. ESMO (Free ESMO Whitepaper) is being held virtually from September 16-21, 2021 (Press release, Tachyon Therapeutics, SEP 17, 2021, View Source [SID1234587904]).

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"Triple negative breast cancer represents nearly 20% of all breast cancers and is a highly aggressive subtype that continues to have poor prognosis due to lack of effective treatments," stated Frank Perabo, MD, PhD, CEO of Tachyon Therapeutics. "Large-scale genomic analysis projects show that KDM4 is amplified in about 25% of triple negative breast cancer cases, making KDM4 an attractive epigenetic target for this cancer type. We are anticipating to study TACH101 in the near future in clinical trials."

Highlights from the ESMO (Free ESMO Whitepaper) abstract are summarized below:

Abstract #210P

TACH101 was potent in killing a Triple Negative Breast Cancer (TNBC) cell line (MDA-MB-231) with an IC50 of 0.0035 µM.
TACH101 treatment of MDA-MB-231 TNBC cells caused cell-cycle arrest and induction of apoptosis with an EC50 of 0.132 µM.
In vivo, TACH101 inhibited tumor growth in the COH70 TNBC xenograft model with tumor growth inhibition > 85%.
Gene expression analysis of TACH101-treated tumors show that Protein Phosphatase 1 Regulatory subunit 10 (PPP1R10 or PNUTS), a key regulator of the retinoblastoma protein (Rb) and p53, was a direct target of KDM4 and was significant downregulated after 24 hours of treatment.
The poster presentation of Abstract #210P is available for viewing on the ESMO (Free ESMO Whitepaper) Annual Meeting website at View Source

On September 17, 2021 Daiichi Sankyo Company, Limited reported New first-in-human data from DS-7300, a B7-H3 directed DXd antibody drug conjugate (ADC) being developed in strategic collaboration with Sarah Cannon Research Institute, showed promising early clinical activity in patients with several types of advanced solid tumors (Press release, Daiichi Sankyo, SEP 17, 2021, View Source [SID1234587903]). These results from the dose escalation portion of a phase 1/2 study of DS-7300 were presented during a Proffered Paper session (#513O) at the European Society for Medical Oncology (#ESMO21) 2021 Virtual Congress.

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B7-H3 is frequently overexpressed in a wide range of cancers including lung, prostate, breast, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma, and its overexpression is associated with poor prognosis.1,2,3 No B7-H3 directed therapies are currently approved for treatment of any cancer.

DS-7300 was tolerated across all dose levels (0.8 mg/kg -16.0 mg/kg) with no dose-limiting toxicities observed in 70 patients enrolled. The most common treatment emergent adverse events (TEAEs) overall in ≥10% of patients were nausea (55.7%), infusion-related reaction (40.0%), decreased appetite (28.6%), vomiting (27.1%), fatigue (21.0%), chills (12.9%), pyrexia (12.9%), dehydration (11.4%) and diarrhea (11.4%). Grade 3 or higher TEAEs regardless of causality occurred in 31.4% of patients (n=22) with the most common being anemia (15.7%) and lymphocyte count decreased (2.8%). One patient receiving the 16.0 mg/kg dose developed interstitial lung disease (ILD) that was associated with death (grade 5) that was adjudicated as treatment related. One case of grade 1 ILD at the 12.0 mg/kg dose that was pending adjudication as of data cut-off of July 21, 2021 has since been adjudicated as treatment related.

Preliminary efficacy results include 15 partial responses (PR), 10 confirmed PRs with 5 additional PRs awaiting confirmation, in patients with a range of solid tumors including metastatic castration-resistant prostate cancer, head and neck squamous cell carcinoma, small cell lung cancer, endometrial cancer, esophageal squamous cell carcinoma and squamous non-small cell lung cancer at doses from 4.8 mg/kg to 16.0 mg/kg. Stable disease has been reported in an additional 32 patients including 24 patients who are still being treated with various doses of DS-7300 as of data cut-off of July 21, 2021. Patients enrolled in the dose escalation study received a median of four prior lines of therapy (range, 1-10).

"These initial safety and efficacy results of DS-7300 are encouraging as we observed that most patients in the study experienced some level of tumor shrinkage," said Melissa Johnson, MD, Director of the Lung Cancer Research Program at Sarah Cannon Research Institute. "Based on these results, we are moving forward with the dose expansion part of the study where we are enrolling patients with metastatic small cell lung cancer, esophageal squamous cell cancer and castration-resistant prostate cancer to further evaluate the potential role of DS-7300 in these cancers."

"These first-in-human results provide preliminary evidence that targeting B7-H3 with DS-7300 may be an effective treatment strategy across several types of cancer where current treatment options are limited," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "Additionally, these results seen with DS-7300, our fourth DXd ADC in clinical development, may further validate the portability of our DXd ADC technology to other targets to create potential new treatments for patients with cancer."

About B7-H3

B7 homologue 3 (B7-H3) is a transmembrane protein belonging to the B7 family. B7-H3 plays a role in tumor growth as well as in immune response.4,5 B7-H3 is frequently overexpressed in various cancers including lung, prostate, breast, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma and its overexpression is associated with poor prognosis.1,2,3

About the DS-7300 Study

This first-in-human, open-label phase 1/2 study is evaluating the safety, tolerability and preliminary activity of DS-7300 in adult patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists.

The first part of the study (dose escalation) is assessing the safety and tolerability of increasing doses of DS-7300 given every three weeks to determine the maximum tolerated dose (MTD) or recommended dose for expansion (RDE). This portion of the trial enrolled 70 patients with advanced/unresectable or metastatic castration-resistant prostate cancer, head and neck squamous cell carcinoma, small cell lung cancer, endometrial cancer, esophageal squamous cell carcinoma, squamous non-small cell lung cancer, breast cancer, melanoma and bladder cancer.

The second part of the study (dose expansion) will be evaluating the safety, tolerability and preliminary activity of DS-7300 at various doses. This portion of the study currently consists of three cohorts of patients with selected advanced/metastatic solid tumors including small cell lung cancer, esophageal squamous cell cancer, and castration-resistant prostate cancer. Additional or alternative indications may be added to expansion cohorts based on preliminary signals of activity.

The study is evaluating safety endpoints including adverse events and efficacy endpoints including objective response rate, duration of response, disease control rate, time to response, progression-free survival and overall survival. Pharmacokinetic endpoints and exploratory biomarker and immunogenicity endpoints also will be assessed.

Patient enrollment into the dose expansion part of the study is underway in Asia and North America. For more information, please visit ClinicalTrials.gov.

About DS-7300

DS-7300 is an investigational B7-H3 directed ADC and is one of six ADCs currently in clinical development in the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, DS-7300 is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker. DS-7300 is being developed through a strategic collaboration with Sarah Cannon Research Institute, with study operational oversight and delivery provided through Sarah Cannon’s early phase Oncology CRO, Sarah Cannon Development Innovations.

DS-7300 is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo in Oncology

The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon, our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.

On September 17, 2021 ImCheck Therapeutics reported that data at the ESMO (Free ESMO Whitepaper) Congress 2021 from its ongoing EVICTION Phase I/IIa clinical trial with its lead antibody ICT01showing anti-tumor immune responses, resulting in increased tumor infiltration and disease control in patients with a variety of relapsed/refractory solid tumors (Press release, ImCheck Therapeutics, SEP 17, 2021, View Source [SID1234587901]). The presentation includes the first data from the trial’s combination cohort of ICT01 plus pembrolizumab in patients who progressed on at least one prior checkpoint inhibitor regimen. Five of the six enrolled patients in the first two dose cohorts were evaluable for efficacy at week eight or beyond. Three of four patients receiving 2 mg ICT01 plus 200 mg pembrolizumab every three weeks (cohort two) achieved disease control: two patients (bladder cancer, metastatic melanoma) showed partial responses and one patient (non-small cell lung cancer) showed stable disease at week 16 or beyond, according to RECIST1.1. Although preliminary, these data provide the first demonstration of clinical responses that are consistent with the observed coordinated antitumor immune response of the innate (γ9δ2 T cells) and adaptive (CD8 T cells) immune systems following ICT01 treatment.

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The data were included in an oral presentation (958O) by Aurélien Marabelle, MD, PhD, Lead Investigator for EVICTION, titled: "Coordinated Activation of Antitumor Responses of γ9δ2 and CD8 T Cells by Targeting BTN3A with ICT01 in Patients with Solid Tumors: EVICTION Trial," on September 17, 2021, from 1:50 – 2:00 pm CET in the Proffered Paper session – Investigational Immunotherapy.

"These data are exciting as they demonstrate for the first time tumor responses in patients treated with ICT01, which continues to support the previously observed immune system activation and good safety profile," commented Aurélien Marabelle, MD, PhD, Immuno-Oncologist at Gustave Roussy, Villejuif, France and Lead Investigator for EVICTION. "Patients in this study are heavily pre-treated, including prior checkpoint inhibitor therapy, and at the stage they join the EVICTION trial have no available standard-of-care treatment options. These preliminary signs of disease control are encouraging and, therefore, we are looking forward to additional data readouts from the EVICTION trial."

"Our anti-BTN3A antibody, ICT01, has already shown promising anti-tumor immune activation and responses so we are cautiously optimistic when reporting today’s preliminary signs of disease control in three patients, including a reduction in tumor burden of up to [~]50% in two of those patients," said Paul Frohna, MD, PhD, Chief Medical Officer at ImCheck Therapeutics. "We remain on target to present additional EVICTION trial data later this year. On behalf of all of us at ImCheck, I want to thank the patients and their families, and the investigators and their clinical study teams for contributing to our study."

The ongoing EVICTION trial is evaluating ICT01 in patients with advanced relapsed/refractory solid and hematologic cancers who have no remaining standard of care treatment options. The presentation today covers results from a dose escalation cohort of evaluable patients with solid tumors (n=32) receiving ICT01 monotherapy and two dose cohorts of evaluable patients with solid tumors (n=6) who previously failed at least one checkpoint inhibitor regimen that were treated with ICT01 in combination with pembrolizumab.

The data from patients with solid tumors treated with ICT01 monotherapy demonstrated a dose-dependent target occupancy of ICT01 binding to BTN3A on T cells that induced a dose-dependent migration of γ9δ2 T cells out of the circulation. Increases in serum TNFα and IFNγ were observed within minutes to hours at doses ≥ 2 mg ICT01 that appear to positively correlate with ICT01 dose, the baseline γ9δ2 T cell counts, and the activation and migration of NK and CD8+ T cells from the circulation. Tumor biopsies showed infiltration of γδ, CD3+ and CD8+ T cells in patients with immune desert at baseline demonstrating the ability to remodel the tumor immune microenvironment across a range of tumor phenotypes. Across the two cohorts treated with a combination of ICT01 and pembrolizumab, preliminary signs of tumor regression were observed at 2 mg ICT01 in two patients. These data may reflect the contribution of ICT01-activated γ9δ2 T cells to remodel the tumor immune microenvironment and increase tumor infiltration of CD8+ T cells, which can be activated by an anti-PD-1 agent like pembrolizumab.

Following multiple safety reviews by the independent Safety Review Committee, the EVICTION trial is continuing further dose escalation in the hematologic monotherapy and combination therapy arms of the study. Part 2 for the monotherapy expansion cohorts is expected to begin enrolling second- and third-line treated patients with ovarian (Group D) or head and neck squamous cell carcinomas (Group E) in Q4 2021. In addition to good preliminary safety, tolerability and immune response data, new results presented at this conference indicate for the first time a beneficial clinical response with signs of tumor shrinkage.

The ESMO (Free ESMO Whitepaper) presentation slides will be available on ImCheck’s corporate website directly following the presentation.

About the EVICTION Trial
EVICTION is a first-in-human, dose escalation (Part 1) and cohort expansion (Part 2) clinical trial of ICT01 in patients with various advanced relapsed or refractory solid or hematologic cancers that have exhausted standard of care treatment options. Part 1 is a basket trial designed to characterize the preliminary safety, tolerability, and pharmacodynamic activity of ICT01 as monotherapy (Group A: solid tumors; Group B: hematologic tumors) and in combination with pembrolizumab (Group C: solid tumors). Group A includes bladder, breast, colorectal, gastric, melanoma, ovarian, prostate, and pancreatic cancer patients, Group B includes acute myeloid leukemia, acute lymphocytic leukemia, follicular lymphoma, and diffuse large B cell lymphoma patients, and Group C includes bladder, head and neck squamous cell carcinoma, melanoma, and non-small cell lung cancer patients. Basket trials are a clinical trial design that allows new drugs to be tested rapidly in a range of indications, providing initial data on multiple parameters that can contribute to an accelerated development timeline. More information on the EVICTION trial can be found at clinicaltrials.gov (NCT04243499).

About ICT01
ICT01 is a humanized, anti-BTN3A (also known as CD277) monoclonal antibody that selectively activates γ9δ2 T cells, which are part of the innate immune system that is responsible for immunosurveillance of malignancy and infections. The 3 isoforms of BTN3A targeted by ICT01 are overexpressed on a number of solid tumors (e.g., bladder, colorectal, melanoma, ovarian, pancreatic, lung) and hematologic cancers (e.g., leukemia & lymphoma) and also expressed on the surface of innate (e.g., γδ T cells and NK cells) and adaptive immune cells (T cells and B cells). BTN3A is essential for the activation of the anti-tumor immune response of γ9δ2 T cells.

As demonstrated in EVICTION data presented at AACR (Free AACR Whitepaper), ICT01 selectively activates circulating γ9δ2 T cells that leads to migration of γ9δ2 T cells out of the circulation and into target tissue (e.g., tumors), while also activating the tumor-resident γ9δ2 T cells to directly kill malignant cells, which is accompanied by secretion of two key inflammatory cytokines, IFNg and TNFa, that contribute to the expansion of the anti-tumor immune response. ICT01 has been shown to have anti-tumor activity against a range of cancers in in vitro and in vivo tumor models.

On September 17, 2021 Novartis reported important findings from a real-world study evaluating the safety and efficacy of alpelisib for people living with PIK3CA-Related Overgrowth Spectrum (PROS) who received treatment daily for at least 24 weeks. Results from EPIK-P1 showed alpelisib effectively reduced volume of clinically significant PROS-related lesions and improved signs and symptoms in pediatric and adult patients (Press release, Novartis, SEP 17, 2021, View Source [SID1234587900]). Results were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2021 [LBA23].

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"There are few options available to manage PROS conditions, and they are mainly focused on addressing worsening symptoms. It is devastating for patients to be without treatments that address the underlying cause of PROS," said Guillaume Canaud, MD, PhD, Necker-Enfants Malades Hospital – AP-HP, the Paris Descartes University, Inserm (INEM Institute Necker Enfants Malades – Centre for Molecular Medicine). "The EPIK-P1 findings show robust clinical benefit for adult and pediatric patients and a potential new path forward for those impacted by PROS conditions."

In EPIK-P1, alpelisib reduced target lesion volume and improved PROS-related symptoms and manifestations. The primary endpoint analysis conducted at week 24 in patients with complete cases (n=32) showed 38% of patients achieving a response to treatment which was defined as 20% or greater reduction in the sum of PROS target lesion volume. Nearly three in four patients (74%) showed some reduction in target lesion volume, with a mean reduction of 13.7%, and no patients experienced disease progression at time of primary analysis.

Additionally, at week 24, investigators reported patient improvements from baseline in pain (90%), fatigue (76%), vascular malformation (79%), limb asymmetry (69%), and disseminated intravascular coagulation (55%) across the full study population (n=57).

"Thanks to the data from patients and physicians included in the analysis of EPIK-P1, we have findings to help validate the potential of alpelisib in PROS and have taken an important step toward reimagining medicine for the PROS community," said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development. "We will continue to discuss this real-world evidence with the FDA in an effort to bring this treatment to people in need as quickly as possible."

Adverse events (AEs) and treatment-related AEs (TRAEs) were experienced by 83% and 39% of patients, respectively. Most AEs were mild to moderate in severity, and there were no AEs leading to treatment discontinuation. The most common AEs of any grade were diarrhea (16%), hyperglycemia (12%), aphthous ulcers (11%), and stomatitis (5%). The most common grade 3/4 AE was cellulitis (4%); one adult case was considered treatment-related.

PROS is a wide-ranging spectrum of disorders caused by a mutation in the PIK3CA gene. PROS conditions are rare and visually diverse, and are typically characterized by atypical growths and anomalies in blood vessels, the lymphatic system and other tissues. PROS conditions can look different from each other in size, shape, and type of growth or malformation based on where in the body the mutation is found.1,2 PROS can disrupt mobility and cognitive function in some patients and may lead to life-threatening complications.3-5

There are no approved medical therapies for PROS conditions. PROS management varies by patient, and surgery and radiologic embolization are common with patients often undergoing multiple procedures due to frequent regrowth following surgery.1,3,4,6-9 There is a significant need for treatment options for PROS that reduce overgrowth, address symptoms, and improve quality of life.3,9-10

The U.S. Food and Drug Administration (FDA) granted alpelisib Breakthrough Therapy Designation on November 13, 2019, and discussions with FDA about alpelisib for PROS are ongoing.

About PIK3CA-Related Overgrowth Spectrum (PROS)
The PROS classification was proposed at the National Institutes of Health in a workshop in 2013 to unite a group of rare overgrowth conditions caused by PIK3CA mutations.1,2 Specific conditions associated with PROS include KTS, CLOVES syndrome, ILM, MCAP/M–CM, HME, HHML, FIL, FAVA, macrodactyly, muscular HH, FAO, CLAPO syndrome and epidermal nevus, benign lichenoid keratosis, or seborrheic keratosis.1,2 The estimated prevalence of PROS conditions is approximately 14 people per million.6 To learn more, visit understandingpros.com.

About EPIK-P1
EPIK-P1 is a global, site-based retrospective non-interventional medical chart review of pediatric and adult male and female patients aged 2 years or older with PIK3CA-Related Overgrowth Spectrum (PROS) who received alpelisib via a compassionate use program. Primary endpoint is proportion of patients with response at 24 weeks, defined as achieving at least 20% reduction from index date in the sum of measurable target lesion volume via central imaging. Data were obtained from medical charts of 57 patients (39 pediatric, 18 adult) at seven sites in five countries. There were 32 complete cases, meaning there were complete scans for comparison at baseline and date of analysis, and one patient discontinued prior to week 24 due to lack of clinical efficacy.

Alpelisib is not approved by any regulatory authority for the treatment of PROS conditions.