On June 4, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, reported that positive interim Phase 1 data from the Company’s FT516 program for patients with relapsed / refractory B-cell lymphoma at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held virtually June 4-8, 2021 (Press release, Fate Therapeutics, JUN 4, 2021, View Source [SID1234583558]). FT516 is the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The ongoing Phase 1 dose-escalation study of FT516 is currently enrolling patients in the fourth dose cohort of 900 million cells per dose.

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As of the data cutoff date of March 11, 2021, four patients in the second dose cohort of 90 million cells per dose and seven patients in the third dose cohort of 300 million cells per dose were evaluable for assessment of safety and efficacy. Eight of eleven patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria (see Table 1). Patients had received a median of three prior lines of therapy and a median of two prior lines containing CD20-targeted therapy. Of the eleven patients, eight patients had aggressive B-cell lymphoma, five patients were refractory to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy.

"These additional data from our Phase 1 study of FT516 administered off-the-shelf in the outpatient setting continue to reinforce its differentiated safety profile and underscore its potential clinical benefit," said Wayne Chu, M.D., Senior Vice President of Clinical Development of Fate Therapeutics. "Based on the favorable therapeutic profile of FT516 that continues to emerge and the potential to treat patients on-demand without delay, we plan to initiate multiple indication-specific, dose-expansion cohorts for patients with B-cell lymphomas to broadly assess FT516 in combination with CD20-targeted monoclonal antibody regimens, including those used as standard-of-care in earlier-line settings."

The ongoing Phase 1 clinical trial in relapsed / refractory B-cell lymphoma is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine), a single-dose of rituximab (375 mg/m2), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting.

Safety Data
No dose-limiting toxicities, and no FT516-related serious adverse events or FT516-related Grade 3 or greater adverse events, were observed. The FT516 treatment regimen was well tolerated, and no treatment-emergent adverse events (TEAEs) of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease were reported by investigators (see Table 2). All Grade 3 or greater TEAEs were consistent with lympho-conditioning chemotherapy and underlying disease. Of note, a Grade 3 or greater TEAE of infection was reported in one patient only. There were no discontinuations due to adverse events, and no patients withdrew from the study except in the setting of disease progression. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting without the need for patient matching.

Activity Data
As of the data cutoff date of March 11, 2021, eleven relapsed / refractory patients in the second and third dose cohorts were evaluable for assessment of safety and efficacy. Of the eleven patients, nine patients completed both FT516 treatment cycles and eight patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria. Notably, two of four patients previously treated with autologous CD19 CAR-T cell therapy achieved a complete response. Two patients showed progressive disease following the first FT516 treatment cycle and discontinued treatment. The Company previously reported that two patients treated in the first dose cohort (30 million cells per dose) showed progressive disease.

Patient Case Study
The ASCO (Free ASCO Whitepaper) presentation featured a case study of a 36-year old male with triple-hit, high-grade B-cell lymphoma with rearrangements of MYC, BCL2, and BCL6 genes. The patient was refractory to all prior lines of therapy with the exception of autologous CD19 CAR T-cell therapy, for which a complete response of two months’ duration was achieved. The patient was most recently refractory to an investigational CD20-targeted T-cell engager and presented with bulky lymphadenopathy with the largest lesion measuring approximately 10 centimeters. The first FT516 treatment cycle resulted in a complete response with resolution of all metabolically active disease and 85% reduction in the size of target lesions. Subsequent to the data cutoff date of March 11, 2021, the patient completed a second FT516 treatment cycle after which the response assessment continued to show complete response.

As of March 11, 2021 database entry. Data subject to source document verification.
CR = Complete Response; PR = Partial Response; PD = Progressive Disease
CAR = Chimeric antigen receptor; DH/DE = Double-hit / double expressor; DLBCL = Diffuse large B-cell lymphoma; FL = Follicular lymphoma;
Gr = Grade; HGBCL = High-grade B-cell lymphoma; iNHL = Indolent non-Hodgkin lymphoma; TH = Triple-hit; Transformed iNHL = Aggressive B-cell lymphoma transformed from indolent non-Hodgkin lymphoma
1 Cycle 2 Day 29 protocol-defined response assessment per Lugano 2014 criteria
2 Subject did not proceed to Cycle 2
3 Confirmed DLBCL (transformation from Gr3A FL) subsequent to the data cutoff date of March 11, 2021
4 Cycle 2 Day 29 protocol-defined response assessment reported subsequent to the data cutoff date of March 11, 2021

CRS = Cytokine Release Syndrome; DL = Dose Level; GvHD = Graft vs. Host Disease; ICANS = Immune Cell-Associated Neurotoxicity Syndrome;
M = Million; SAE = Serious Adverse Event; TEAE = Treatment-Emergent Adverse Event
1 Includes two subjects in the first dose cohort of 30 million cells per dose

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Scientists from the Company have shown in a peer-reviewed publication (Blood. 2020;135(6):399-410) that hnCD16 iPSC-derived NK cells, compared to peripheral blood NK cells, elicit a more durable anti-tumor response and extend survival in combination with anti-CD20 monoclonal antibodies in an in vivo xenograft mouse model of human lymphoma. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

On June 4, 2021 Alkermes plc (Nasdaq: ALKS) reported new data from its ARTISTRY clinical development program for nemvaleukin alfa (nemvaleukin), Alkermes’ novel, investigational engineered interleukin-2 (IL-2) variant immunotherapy. The data are being presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place virtually June 4-8, 2021, and in an investor webcast presentation hosted by the company (Press release, Alkermes, JUN 4, 2021, View Source [SID1234583574]).

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The presentations include updated efficacy and safety data from ARTISTRY-1, an ongoing phase 1/2 study investigating intravenous (IV) nemvaleukin, which showed anti-tumor activity of IV nemvaleukin monotherapy in checkpoint inhibitor (CPI)-experienced melanoma and renal cell carcinoma (RCC) patients, and anti-tumor activity of IV nemvaleukin in combination with pembrolizumab in a range of difficult-to-treat tumors, including in CPI-unapproved tumor types, and in CPI-approved tumor types among both CPI treatment-naïve and pretreated patients. Durable and deepening responses have been observed with IV nemvaleukin, as monotherapy or in combination with pembrolizumab, in platinum-resistant ovarian cancer (PROC) and mucosal melanoma. Treatment-related adverse events (AEs) were mostly transient and manageable and the maximum tolerated dose had not yet been reached.

Alkermes’ presentations also include data from ARTISTRY-2, an ongoing phase 1/2 study evaluating subcutaneous (SC) nemvaleukin. Findings include a pharmacodynamic response and safety profile that support the recommended phase 2 dose (RP2D), and encouraging early signs of anti-tumor activity in PROC.

"Intravenous nemvaleukin’s observed single-agent activity in melanoma and renal cell carcinoma, and combination activity in both PD-1/L1 unapproved and approved tumor types, support its potential to be a treatment option for a range of difficult-to-treat cancers," said Valentina Boni, M.D., Ph.D., Lead Investigator, ARTISTRY-1 and Medical Oncologist Principal Investigator START Madrid at Centro Integral Oncológico Clara Campal. "In the ARTISTRY-1 trial, the durable and deepening responses observed in PROC and mucosal melanoma are particularly encouraging as these patients have limited treatment options."

"ARTISTRY-1 and ARTISTRY-2 have yielded important clinical data that will guide and serve as the foundation for future clinical evaluation of nemvaleukin. As the data have evolved, we have seen new objective responses in a range of tumors, and improvements upon certain previously reported responses, which provide additional support for nemvaleukin’s potential utility," said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President of Research & Development at Alkermes. "We are proud to participate in the important dialogue at this year’s Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and are committed to the development of medicines that seek to improve treatment outcomes for people affected by cancer, particularly cancers for which there are limited or no treatment options currently available."

Data highlights from the ASCO (Free ASCO Whitepaper) poster presentations and the company’s investor presentation include:

ARTISTRY-1, IV Nemvaleukin Monotherapy Cohort
The ARTISTRY-1 monotherapy cohort included CPI-experienced patients with melanoma and renal cell carcinoma. Data are as of March 19, 2021 unless otherwise noted:

Melanoma monotherapy cohort: Among 30 total evaluable patients, 24 continued on study, including 13 patients who rolled over to a combination cohort evaluating nemvaleukin in combination with pembrolizumab.
Metastatic mucosal melanoma: 2 out of 6 patients achieved a partial response (PR) (one unconfirmed). The patient with the confirmed PR demonstrated a durable, deepening response and had been on treatment for 74 weeks.
Cutaneous melanoma: 2 out of 18 evaluable patients achieved a PR (one unconfirmed, one awaiting confirmation), as of May 3, 2021.
Stable disease (SD) was observed in 21 patients.
RCC monotherapy cohort: Among 20 evaluable patients, 12 continued on study, including 6 who rolled over to a combination cohort.
2 patients achieved a PR (one awaiting confirmation as of May 3, 2021) and SD was observed in 10 patients.
ARTISTRY-1, IV Nemvaleukin in Combination with Pembrolizumab
The combination cohorts in ARTISTRY-1 included: patients with PD-1/L1 unapproved tumor types; patients with PD-1/L1 approved tumor types (PD-1/L1 pretreated and PD-1/L1 treatment naïve); patients in tumor-specific cohorts; and patients who rolled over from monotherapy cohorts. Data are as of May 3, 2021:

Among the total 100 evaluable patients in the combination cohorts, 19 objective responses were observed.
Out of the 14 evaluable patients with ovarian cancer enrolled in the PD-1/L1 unapproved cohort, there was 1 complete response (CR), 3 PRs (one unconfirmed) and 6 had SD. As of the data cut, 3 of the 4 patients with objective responses had been on treatment for more than a year and continued on therapy.
Out of the 4 evaluable patients with cervical cancer enrolled in the PD-1/L1 approved cohort, 2 achieved a PR (one awaiting confirmation). As of the data cut, 3 out of the 4 evaluable patients continued on therapy.
Objective responses were also observed in patients with the following cancers: esophageal, bladder, Hodgkin’s lymphoma, breast, RCC, mucosal melanoma, colorectal, gastric, pancreatic, head and neck, small cell and non-small cell lung.
As of March 19, 2021, treatment-related AEs across the monotherapy and combination cohorts were consistent with expectations based on nemvaleukin’s mechanism of action and were mostly transient and manageable at the IV RP2D of 6 µg/kg. Pyrexia, chills and nausea were the most commonly reported AEs. Transient and asymptomatic neutropenia/neutrophil count decrease were the most commonly reported events of grade ≥3. Nemvaleukin, whether as monotherapy or in combination with pembrolizumab, demonstrated no additive toxicity to that established with pembrolizumab alone.

ARTISTRY-2, SC Nemvaleukin Study
The dose-escalation stage of ARTISTRY-2 evaluated the safety and tolerability of ascending doses of SC nemvaleukin administered once weekly (q7d) or once-every-three-weeks (q21d) as lead-in monotherapy for six weeks, followed by combination with pembrolizumab. The ongoing efficacy-expansion stage of ARTISTRY-2 is examining the safety and efficacy of SC nemvaleukin administered at the RP2D in combination with pembrolizumab in select solid tumors. Data are as of March 19, 2021 unless otherwise noted:

SC 3 mg q7d nemvaleukin was selected as the RP2D for the efficacy expansion stage following its demonstration of pharmacodynamic effects on Natural Killer (NK) cells and CD8+ T cells, with minimal expansion of regulatory T cells (Tregs), and a safety and tolerability profile largely consistent with the anticipated pharmacological effect and that observed with IV nemvaleukin.
Phase 2 expansion cohorts at the RP2D recently opened for enrollment. As of May 3, 2021, one confirmed PR had been observed in a patient with PROC, with a 53% reduction in target lesion and a normalization of CA-125 levels.
The safety profile of SC nemvaleukin was largely consistent with that reported for IV nemvaleukin. The most common AEs were pyrexia, fatigue, chills and injection site reactions. Three dose-limiting toxicities were reported, all in the highest doses evaluated in each dosing regimen (declared as the maximum tolerated dose). No additive toxicity was observed with the addition of pembrolizumab to the SC treatment regimen.

Data from both presentations are available on the ASCO (Free ASCO Whitepaper) website at View Source

Abstract: 2513
Title: ARTISTRY-1: Nemvaleukin Alfa Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
Presenter: Valentina Boni, M.D., Ph.D., Medical Oncologist and Principal Investigator, START Madrid at Centro Integral Oncológico Clara Campal, Madrid, Spain
Presentation Date/Time: The on-demand poster discussion session will take place on June 4, 2021 at 9:00 a.m. ET

Abstract: 2552
Title: Selection of the Recommended Phase 2 Dose (RP2D) for Subcutaneous Nemvaleukin Alfa: ARTISTRY-2
Presenter: Omid Hamid, M.D., Chief of Research and Immunotherapy, The Angeles Clinic and Research Institute
Presentation Date: The poster presentation will be available on-demand to attendees beginning June 4, 2021

Conference Call and Webcast
Alkermes will host a webcast presentation and conference call with accompanying slides for analysts and investors on Friday, June 4, 2021, at 4:00 p.m. ET (9:00 p.m. BST) to discuss the latest data from the ARTISTRY-1 and ARTISTRY-2 clinical trials. The webcast will feature ARTISTRY clinical program investigators, Valentina Boni, M.D., Ph.D., Medical Oncologist and Principal Investigator, START Madrid at Centro Integral Oncológico Clara Campal; and Omid Hamid, M.D., Chief of Research and Immunotherapy, The Angeles Clinic and Research Institute, and members of Alkermes’ management team. The webcast player may be accessed on the Investors section of Alkermes’ website at www.alkermes.com. To participate in the question-and-answer session, please also dial in to the conference call, which may be accessed by dialing +1 877-407-2988 for U.S. callers and +1 201-389-0923 for international callers. A replay of the webcast will be archived on the company’s website for 30 days following the presentation.

About Nemvaleukin Alfa ("nemvaleukin")
Nemvaleukin is an investigational, novel, engineered fusion protein comprised of modified interleukin-2 (IL-2) and the high affinity IL-2 alpha receptor chain, designed to selectively expand tumor-killing immune cells while avoiding the activation of immunosuppressive cells by preferentially binding to the intermediate-affinity IL-2 receptor complex. The selectivity of nemvaleukin is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while mitigating certain limitations.

About the ARTISTRY Clinical Development Program
ARTISTRY is an Alkermes-sponsored clinical development program evaluating nemvaleukin alfa as a potential immunotherapy for cancer. The ARTISTRY program is comprised of multiple clinical trials evaluating intravenous and subcutaneous dosing of nemvaleukin, both as a monotherapy and in combination with the anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with advanced solid tumors. Ongoing trials include: ARTISTRY-1, ARTISTRY-2, ARTISTRY-3 and ARTISTRY-6.

On June 4, 2021 Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company developing a new class of potent and selective precision oncology medicines, which it refers to as Pentarin miniature drug conjugates, reported data from the gastrointestinal (GI) mid-gut neuroendocrine tumors (NETs) cohort of its Phase 2 clinical trial of PEN-221, presented at the 2021 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Tarveda Therapeutics, JUN 4, 2021, businesswire.com/news/home/20210604005111/en/Tarveda-Therapeutics-Presents-Promising-Phase-2-Data-of-PEN-221-in-Gastrointestinal-Mid-gut-Neuroendocrine-Tumors [SID1234583590]).

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"The results presented at ASCO (Free ASCO Whitepaper) from the gastrointestinal mid-gut neuroendocrine cohort of the PEN-221 trial show that PEN-221 was well tolerated and demonstrated efficacy exceeding its clinical efficacy goals with a clinical benefit rate of 88.5% and median progression-free survival of 9 months," said Jeffrey Bloss, M.D., Chief Medical Officer of Tarveda. "We are encouraged by the safety and efficacy shown by PEN-221 in GI mid-gut NETs and are developing a randomized trial to further evaluate PEN-221 in this patient population."

"Gastrointestinal neuroendocrine tumors are a disease with a significant unmet need. While targeting SSTR2 receptors has been an effective strategy in treating GI NETs, there remains a need for additional therapies which delay disease progression and prolong patients’ lives," said Daniel M Halperin, M.D., Assistant Professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. "PEN-221 selectively binds with high affinity to SSTR2 expressed on neuroendocrine tumors, where it releases its DM1 payload directly into the tumor cells, causing cell cycle arrest and apoptosis. This approach demonstrated encouraging efficacy results in the GI mid-gut NET cohort of the Phase 2 trial and was well tolerated by patients."

The results presented had a data cutoff of July 31, 2020 and five patients remained on study at the time of the cutoff. Of the 32 patients included in these results, the first nine were treated at the Phase 1 determined maximum tolerated dose of 18 mg. After review of the safety, tolerability, and pharmacokinetic data, the regimen was amended to 8.8 mg/m2 for all subsequent patients to achieve more uniform exposures across all patients and reduce toxicity in patients with lower body-surface-area (BSA).

Trial Design

PEN-221 was administered as a one-hour intravenous infusion once every three weeks to patients with advanced SSTR2+ GI mid-gut NETs with documented radiographic progression within the six months prior to enrollment. Preliminary efficacy was assessed using RECIST 1.1. A clinically meaningful efficacy result was defined as a clinical benefit rate (CBR) > 75% and a median progression-free survival (mPFS) > 8 months.

Safety Data

A safety analysis of 32 patients demonstrated that PEN-221 was well tolerated when dosed at 8.8 mg/m2. The most frequent treatment related adverse events of any Grade were fatigue (39%), nausea (38%), diarrhea (35%), decreased appetite (30%), infusion reaction (24%), aspartate transaminase (AST)/alanine transaminase (ALT)/alkaline phosphatase (Alk Phos) increase (24%), and peripheral neuropathy (21%). Only 14 (10%) of these events were Grade 3 or greater. Grade 3 treatment related adverse events, which were reported in two or more patients, included fatigue (7.6%), ALT/AST/Alk Phos increase (7.6%), and peripheral neuropathy (3%).

Efficacy Data

PEN-221 demonstrated efficacy at 8.8 mg/m2 with a CBR of 88.5% and mPFS of 9 months. Of the 26 patients who were evaluable for response, 23 (88.5%) had stable disease (SD) reported as their best response and target lesion shrinkage was observed in 10 (38%) patients.

A randomized trial of PEN-221 in GI mid-gut NET patients is now in development.

The poster presentation is available on demand on the ASCO (Free ASCO Whitepaper) website beginning on June 4, 2021 at 9:00 AM ET. Details of the poster presentation are as follows:

Title: The safety and efficacy of PEN-221 somatostatin analog (SSA)-DM1 conjugate in patients (PTS) with advanced GI mid-gut neuroendocrine tumor (NET): Phase 2 results.
Abstract Number: 4110

About PEN-221

PEN-221 is a miniature drug conjugate consisting of a peptide ligand, that is highly selective in targeting SSTR2, joined through a cleavable linker to the potent cytotoxic payload DM1. SSTR2 is overexpressed on the cell surface of a range of solid tumors including neuroendocrine tumors and small cell lung cancers. In non-clinical experiments, PEN-221 binds with high affinity and selectivity to SSTR2. On binding, PEN-221 triggers SSTR2 internalization resulting in the accumulation of the DM1 payload in tumor cells followed by cell cycle arrest and apoptosis.

PEN-221 is being evaluated in Phase 2a expansion cohorts enrolling patients with mid-gut neuroendocrine tumors, pancreatic neuroendocrine tumors, and small cell lung cancer (ClinicalTrials.gov Identifier: NCT02936323).

On June 4, 2021 GRAIL, Inc., a healthcare company whose mission is to detect cancer early, reported the first results from the interventional PATHFINDER study evaluating Galleri, a multi-cancer early detection (MCED) blood test. The results, presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, support Galleri’s performance in clinical settings (Press release, Grail Bio, JUN 4, 2021, View Source [SID1234583644]). The company also announced today that Galleri is now available in the U.S. by prescription only.

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"The interim results of PATHFINDER demonstrate that a routine blood test is capable of detecting many different cancers even before symptoms arise, an approach that has significant potential advantages," said Dr. Tomasz M. Beer, deputy director at the OHSU Knight Cancer Institute and presenting author. "Most importantly, it can detect cancers that have no recommended screening tests today, and more than two-thirds of cancers go unscreened for this reason. These results are a pivotal step toward extending early detection to many more types of cancer."

Clinical Data from PATHFINDER

PATHFINDER was designed to assess the implementation and performance of Galleri in a clinical care setting, evaluate the clinical care pathways following a "signal detected" Galleri test result, and measure the time required to achieve diagnostic resolution.

The study analyzed 6,629 individuals aged 50 years or older, an age group at elevated risk for cancer, but with no suspicion of active cancer. Compared to the general population, participants had equal or higher compliance with recommended breast and colon cancer screening tests.

In the interim analysis, an earlier version of Galleri accurately detected 29 cancers across 13 types: breast, colon or rectum, head and neck, liver and bile duct, lung, lymphoid leukemia, lymphoma, ovary, pancreas, plasma cell neoplasm, prostate, small intestine, and Waldenstrom macroglobulinemia. Of the new cancers detected, nearly 40% (9/23) were localized (stage I-II), and more than half (13/23) were detected before distant metastases (stage I-III). PATHFINDER participants will continue to be followed for 12 months, with final results expected in the first half of 2022.

"Finding cancer early, when treatment is more likely to be successful, is one of the most significant opportunities we have to reduce the burden of cancer," said Dr. Joshua Ofman, chief medical officer and head of external affairs at GRAIL. "These data suggest that, if used at scale alongside existing screening tests, the Galleri test could have a profound impact on how cancer is detected and, ultimately, on public health."

The interim PATHFINDER positive predictive value (PPV), or the likelihood that a person has cancer when a positive test result is returned, was 44.6% (95% CI: 33.2-56.7%), which is consistent with findings from GRAIL’s case-controlled Circulating Cell-free Genome Atlas (CCGA) Study.

When cancer was confirmed, Galleri’s first or second cancer signal origin prediction was 96.3% accurate (95% CI: 81.7-99.8%), with a median observed time to cancer diagnosis of 50 days. The interim analysis identified only four study-related adverse events (two related to mild anxiety before the test, one related to mild anxiety about the blood draw, and one related to mild bruising).

"Early cancer detection is critical to reducing the burden of cancer-related morbidity and mortality. These results reflect the potential real-world ability of Galleri to find deadly cancers earlier, and represent a leap forward in the effort to treat cancer more effectively," Dr. Beer said.

Data is presented by Dr. Beer, and the presentation will be available at View Source

Introducing Galleri

Galleri is now available in the U.S. by prescription only. The Galleri test is intended for use in those with an elevated risk of cancer, such as adults aged 50 or older, and as a complement to existing single cancer screening tests.

In an observational study, Galleri has demonstrated the ability to detect more than 50 types of cancer, over 45 of which lack recommended screening tests today in the U.S., with a low false positive rate of less than 1%. When cancer is detected, Galleri can determine the cancer signal origin with high accuracy. New CCGA data published today in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), also demonstrate the ability of GRAIL’s technology to preferentially detect cancers that are more aggressive than expected based on age, and the cancer stage and type.

The blood test is supported by what is believed to be the largest clinical study program in genomic medicine, with over 140 clinical study sites, including the Mayo Clinic, Dana-Farber Cancer Institute, Cleveland Clinic, Sutter Health, OHSU, Intermountain Healthcare, and U.S. Oncology Research.

Cancer is expected to become the leading cause of death in the United States this year, in large part because the majority of cancers are found too late when outcomes are poor. Recommended screening tests save lives, but only cover five cancer types in the U.S. In fact, 71% of cancer deaths in the U.S. have no recommended early detection screening.

For more information about Galleri, visit www.galleri.com.

REFLECTION Registry

GRAIL also announced it will establish a real-world evidence study, REFLECTION, to understand the experience and clinical outcomes of 35,000 individuals in the U.S. who are prescribed the Galleri test from a healthcare provider. This follows an announcement last fall that Galleri will be offered to eligible patients in the United Kingdom (UK) later this year as part of a partnership with the UK National Health Service to support its Long Term Plan for earlier cancer diagnoses.

Important Safety Information

Galleri is recommended for use in adults with an elevated risk for cancer, such as those aged 50 or older. The Galleri test does not detect all cancers and should be used in addition to routine cancer screening tests recommended by a healthcare provider. Galleri is intended to detect cancer signals and predict where in the body the cancer signal is located.

Results should be interpreted by a healthcare provider in the context of medical history, clinical signs, and symptoms. A test result of ​"Cancer Signal Not Detected" does not rule out cancer. A test result of ​"Cancer Signal Detected" requires confirmatory diagnostic evaluation by medically established procedures (e.g., imaging) to confirm cancer.

If cancer is not confirmed with further testing, it could mean that cancer is not present or testing was insufficient to detect cancer, including due to the cancer being located in a different part of the body. False positive (a cancer signal detected when cancer is not present) and false negative (a cancer signal not detected when cancer is present) test results do occur. Galleri is prescription only.

Laboratory/Test Information

GRAIL’s clinical laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and accredited by the College of American Pathologists (CAP). The Galleri test was developed, and its performance characteristics were determined by GRAIL. The Galleri test has not been cleared or approved by the U.S. Food and Drug Administration. GRAIL’s clinical laboratory is regulated under CLIA to perform high-complexity testing. The Galleri test is intended for clinical purposes.

On June 4, 2021 BerGenBio ASA (OSE:BGBIO), BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported that end-of-trial data from a Phase I/II study of bemcentinib in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, BerGenBio, JUN 4, 2021, View Source [SID1234583870]).

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Study Design

Phase I of the study was a dose escalation arm designed to confirm the safety and tolerability of bemcentinib in NSCLC patients as both monotherapy and in combination with erlotinib in patients whose disease had previously progressed on erlotinib alone.

Phase II assessed patients in two groups; those whose disease had progressed on an approved EGFR inhibitor, and those who were responding/stable on erlotinib as a first line treatment. Both groups were treated with bemcentinib and erlotinib to evaluate the safety and activity of the combination, while assessing reversal or prevention of resistance to EGFR inhibition.

Conclusions

Data from the study found that Bemcentinib in combination with erlotinib was well tolerated over extended periods of time, with the longest ongoing patients having been dosed for over 46 months.

The combination led to disease stabilisation and durable tumour responses in a proportion of patients who had previously progressed on EGFR targeted therapy and who were negative for the T790M resistance mutation. In patients who were responding to first line treatment with erlotinib, either stable disease or partial response, the addition of bemcentinib led to further deepening of responses and prolonged the duration of responses beyond 30 months in 4 out of the 13 patients evaluated.

At the time of data cut-off, 2 patients are still participating in the study beyond 34 months of treatment. Ongoing patients at the time of study closure, who wish to continue receiving study treatment, will be offered the drug via an expanded access program.

Presenting author Lauren Byers, M.D., associate professor of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center, in Houston, said: "We are encouraged by the responses observed both in patients whose disease was progressing on EGFRi alone, as well as patients already in remission with erlotinib. In particular we were pleased to see durable responses exhibited by a number of patients on the study, with two patients continuing to be dosed with bemcentinib beyond 36 months. This is a good indicator that
bemcentinib offers excellent tolerability as well as the potential for anti-tumour activity and we look forward to following their progress as their treatment continues"

Byers reports past advisory board participation for BerGenBio.

Richard Godfrey, CEO of BerGenBio, said: "This end of study data shows the potential of bemcentinib as a combination treatment alongside EGFR inhibitors such as erlotinib and osimertinib, which are established treatments and widely used in indications such as NSCLC in patients with the EGFR driver mutation. We believe that further clinical investigation is needed to fully explore this potential, and look forward to discussing our findings further with our colleagues at ASCO (Free ASCO Whitepaper)."

Details of the presentation, also available on the investor section of BerGenBio’s website, are as follows:

E-poster title: Ph I/II study of oral selective AXL inhibitor bemcentinib (BGB324) in combination with erlotinib in patients with advanced EGFRm NSCLC: end of trial update

Session: Lung Cancer – Non-Small Cell Metastatic

Abstract ID: 9110

Date/Time: Friday, June 4, 2021 at 9:00 AM (EDT)

Authors: Byers et al.

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases.

In COVID-19, AXL has two synergistic mechanisms of action, it acts a co-receptor to ACE2, to which the spike protein of the SARS-CoV-2 virus attaches and enters the host cell, and AXL expression is upregulated that leads to suppression of the Type 1 Interferon immune response by host cells and in their environment.

Research data confirms bemcentinib inhibits SARS-CoV-2 host cell entry and promotes the anti-viral Type I interferon response. Data from a Phase II in human clinical trial has shown that treatment with AXL inhibitor bemcentinib increased the rate ventilator free survival in hospitalised COVID-19 patients.

In cancer, increase in AXL expression has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers. AXL suppresses the body’s immune response to tumours and drives treatment failure across many cancers. High AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, such as bemcentinib, therefore, have potential high value as monotherapy and as the cornerstone of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases including fibrosis.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potential first-in-class, potent and highly selective AXL inhibitor, currently in a broad phase II clinical development programme. It is administered as an oral capsule and taken once per day. Ongoing clinical trials are investigating bemcentinib in COVID-19, and multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity.