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 (Press release, Grail Bio, JUN 4, 2021, View Source [SID1234583577]). The results, presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, support Galleri’s performance in clinical settings. 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 cancer1, 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.

On June 4, 2021 Pacylex Pharmaceuticals, an oncology company unlocking a new approach to cancer therapy, and Greenfire Bio, a new Life Science development and investment company, reported the closing of Series A financing for Pacylex (Press release, Greenfire, JUN 4, 2021, View Source [SID1234583545]). These funds will be used to support the initial Phase 1 clinical investigation of PCLX-001, a first-in-class N-myristoyltransferase (NMT) inhibitor, in Diffuse Large B-Cell Lymphoma and solid tumor patients. Pacylex is leading the development of novel therapies targeting the biological process of myristoylation in cancer.

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"We are excited to be a catalyst for this new innovation in oncology" said Ajit Gill, CEO of Greenfire Bio. "Our goal is to build a portfolio of potential breakthroughs in medicine, and we look forward to seeing PCLX-001 move into the clinic."

"The support from Greenfire Bio is essential for our transformation into a clinical stage company", said Michael Weickert, CEO of Pacylex. "Pioneering a new target and first-in-class therapy is extraordinarily important to expand cancer treatment options and improve patient outcomes. We are delighted to find the right investor with an appreciation for this groundbreaking work."
Clinical site preparations are underway for the open label, dose escalation, Phase 1 clinical trial, principally to evaluate the safety of PCLX-001. The study will enroll 20-30 patients and the Company anticipates that enrollment will begin within the next month. A No Objection Letter from Health Canada was received by Pacylex on March 8, 2021, authorizing the planned Phase 1 Trial of PCLX-001 in relapsed/refractory B-cell Non-Hodgkin Lymphoma and advanced solid malignancies. PCLX-001 is believed to be the first NMT inhibitor that will be clinically tested. Three principal investigators will oversee the clinical study at three clinical sites in Canada: Dr. John Kuruvilla at Princess Margaret Cancer Centre in Toronto, Dr. Randeep Sangha at the Cross Cancer Institute in Edmonton and Dr. Laurie Sehn at the British Columbia Cancer Center in Vancouver.

PCLX-001

PCLX-001 is a small molecule, first-in-class NMT inhibitor, originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness funded by Wellcome Trust. Pacylex is developing PCLX-001, which has excellent oral bioavailability, to treat leukemia and lymphoma. PCLX-001 selectively kills cancer cells and completely regresses (eliminates) tumors in animal models of acute myeloid leukemia (AML), diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). PCLX-001 has also been shown to inhibit the growth of lung and breast cancer tumors in animal models. In leukemia, lymphoma and breast cancer patients, the level of NMT2 is correlated with survival, suggesting an important biological role in these cancers. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as ibrutinib (Imbruvica) and dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.

On June 4, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported interim efficacy data, as of an April 13, 2021 cutoff date, from the phase 1/2 eNRGy trial and Early Access Program (EAP) of bispecific antibody zenocutuzumab (Zeno) in patients with NRG1+ cancers, presented virtually by Lead Author, Dr. Alison Schram of Memorial Sloan Kettering Cancer Center (MSKCC) at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Merus, JUN 4, 2021, View Source [SID1234583576]).

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Dr. Andrew Joe, Chief Medical Officer at Merus said, "With confirmed partial responses observed in 42% of pancreatic cancer patients, and partial responses across several NRG1+ tumor types, we remain encouraged that Zeno has the potential to become a new treatment for patients with NRG1 fusion positive cancers. The data, including durability, continue to mature with 40% of evaluable patients remaining on therapy as of the data cutoff date."

Dr. Alison Schram said, "It is very exciting to witness the emergence of a potential new treatment for patients with NRG1 fusion-positive cancers, a population with unmet need. The data presented today are the first to clinically validate NRG1 fusions as drivers of cancer and show that Zeno is capable of blocking tumor growth in patients harboring these fusions."

The reported data are from the ongoing phase 1/2 eNRGy trial and EAP which are investigating the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancers. The eNRGy trial consists of three cohorts: NRG1+ pancreatic cancer; NRG1+ non-small cell lung cancer (NSCLC); and NRG1+ other solid tumors.

Key findings in the presentation include:

Enrollment of 61 patients with NRG1+ pancreatic, NSCLC, and other cancers.
47 patients were evaluable for primary analysis , with a median age of 56 (range 22-84), previously treated with a median of 2 lines of prior therapy.
45 patients were evaluable for response by local review with measurable disease and the opportunity for ≥ 1 post-baseline tumor assessment (two patients with non-measurable disease are included in the primary analysis of 47 patients, but not included in the 45 evaluable for response).
Partial responses (PRs) achieved across four different NRG1+ tumor types and multiple different fusion partners
Across NRG1+ tumor types, 29% overall response rate (ORR) with 13 of 45 achieving PRs, one additional unconfirmed PR was confirmed after the April 13, 2021 data cutoff date (14 of 45, 31%); median duration of exposure is 5.5 months, with 40% of evaluable patients continuing on treatment; the duration of response ranges from 1+ to approximately 12 months.
34 of 45 (76%) patients had tumor reduction
42% ORR with 5 of 12 PRs in pretreated NRG1+ pancreatic cancer
Median duration of exposure as of the April 13, 2021 data cut-off is 5.7 months, with 7 of 12 patients continuing on treatment.
In NSCLC, 25% ORR, with 6 of 24 PRs; one additional unconfirmed PR was confirmed after the data cutoff date (7 of 24, 29%).
Among all other solid tumors, 22% ORR with 2 of 9 PRs.
Zeno was observed to have a favorable and tolerable safety profile (across 157 patients treated with Zeno monotherapy as of the Jan 12, 2021 safety data cutoff date).
The majority of adverse events were mild or moderate (Grade 1 or 2) in severity.
Absence of severe gastrointestinal and skin toxicities and clinical cardiotoxicity.
Low incidence (7%) of infusion reactions
First prospective clinical validation of NRG1 fusions as actionable oncogenic drivers that may be amenable to targeted therapy with Zeno.
Merus plans the next program and clinical update for Zeno at a major medical conference by the first half of 2022.

Company Conference Call and Webcast Information

Merus will hold a conference call and webcast for investors on Sunday, June 6, 2021 at 6:00 PM ET to discuss the Zeno clinical data. A replay will be available after the completion of the call in the Investors and Media section of our website.

Date: Sunday, June 6 at 6:00 pm ET
Webcast link: available on our website
Dial-in: Toll-Free: 1-877-260-1463 / International: 1-706-643-5907
Conference ID: 9678617

About the eNRGy Clinical Trial
Merus is currently enrolling patients in the phase 1/2 eNRGy trial to assess the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancers. The eNRGy trial consists of three cohorts: NRG1+ pancreatic cancer; NRG1+ non-small cell lung cancer; and NRG1+ other solid tumors. Further details, including current trial sites, can be found at www.ClinicalTrials.gov and Merus’ trial website at www.nrg1.com or by calling 1-833-NRG-1234.

About Zeno
Zeno is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 gene fusions (NRG1+). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancers. In preclinical studies, Zeno also potently inhibits HER2/HER3 heterodimer formation and tumor growth in models harboring NRG1 fusions.

On June 4, 2021 Provectus (OTCQB: PVCT) reported that preliminary full study data from the Company’s Phase 1 clinical trial of investigational cancer immunotherapy PV-10 (rose bengal disodium) for the treatment of neuroendocrine tumors (NET) metastatic to the liver (mNET) refractory to somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) (NCT02693067) is be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, held June 4-8 online (Press release, Provectus Biopharmaceuticals, JUN 4, 2021, View Source [SID1234583575]).

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Highlights from the mNET Presentation at ASCO (Free ASCO Whitepaper) 2021:

Baseline and disease characteristics
12 patients; 50% male; median age of 66 years (range 47-79)
Primary tumor sites: 7 small bowel (58%), 2 pancreas (17%), 1 caecal (8%), and 2 unknown (17%)
NET grades: 5 Grade 1 (42%) and 7 Grade 2 (58%)
Refractory to SSA and PRRT; symptomatic progressive disease
PV-10 treatment summary
Median of 1 hepatic NET lesion injected (range 1-4); median of 1 injection cycle (range 1-4); 8 patients (75%) received 1 PV-10 treatment
Safety
Mild-to-moderate post-procedure pain reported by most patients
Grade 3 photosensitivity reaction in 1 patient, Grade 3 elevation of hepatic enzymes in 1 patient, and carcinoid flare in 2 patients
Injected lesion efficacy (RECIST 1.1)
42% partial response (PR) and 42% objective response rate (ORR)
Patient-level efficacy (RECIST 1.1)
83%a disease control rate (DCR)
Progression-free survival (PFS): median 9.2 months (range 1.0-41.8)
Overall survival (OS): median 22.5 months (range 5.5-41.8); 6 patients (50%) undergoing response follow-up at the data cut-off of April 30, 2021
Immune response
Upregulation of NK cells and activated CD4+ T cells was observed in peripheral blood collected 7 and 28 days post-PV-10 injection
Biomarkers and quality of life (QOL)
Chromogranin A levels remained stable in 10 patients (83%)
QOL assessments showed stable or improved carcinoid symptoms and global health status in most patients
a Typographical error on the poster

A copy of the poster is available on Provectus’ website at View Source

This clinical trial, a single-center study at The Queen Elizabeth Hospital (TQEH) in Adelaide, Australia that completed enrollment in 2020, is led by Tim Price, MBBS, DHlthSc (Medicine), FRACP, Head of Clinical Oncology Research and Chair of the combined Hematology and Medical Oncology Unit at TQEH and Clinical Professor in the Faculty of Medicine at the University of Adelaide. The primary endpoint of the trial is safety. Secondary endpoints include ORR of injected target and measurable bystander lesions, target lesion somatostatin receptor expression, and biochemical response. Disease response assessments are conducted by independent review using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Six patients in the first cohort each received one percutaneously-administered injection of PV-10 to one target lesion per treatment cycle. Patients in the six-person second cohort can receive PV-10 injections of multiple lesions per cycle.

Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, said, "The vast majority of patients with neuroendocrine cancer present with liver metastases, and their prognosis is poor. PV-10 treatment of these hepatic tumors in heavily pre-treated patients resulted in durable systemic clinical benefit and evidence of immunotherapeutic activity in an otherwise immunologically cold tumor type."

Mr. Rodrigues added, "Provectus’ PV-10 development program for visceral hepatic tumors, led by more recent clinical study of neuroendocrine cancer and uveal melanoma, has not elicited any safety concerns and provided encouraging evidence of local and systemic response and disease control in refractory patient populations. Numerous liver metastases of defined tumor types have been treated in this program, including hepatoma, colorectal, lung, pancreatic, ovarian, cutaneous melanoma, breast, neuroendocrine, and uveal melanoma."

About PV-10

Intralesional (IL) administration of PV-10 for the treatment of solid tumor cancers can yield immunogenic cell death within hours of tumor injection, and induce tumor-specific reactivity in circulating T cells within days.1,2,3 This IL PV-10-induced functional T cell response may be enhanced and boosted in combination with immune checkpoint blockade (CB).4 In CB-refractory advanced cutaneous melanoma, IL PV-10 may restore disease-specific T cell function, which may also be prognostic of clinical response. IL PV-10 has been administered to over 450 patients with cancers of the skin and of the liver. It is administered under visual, tactile or ultrasound guidance to superficial malignancies, and under CT or ultrasound guidance to tumors of the liver. Systemic administration of PV-10 is also undergoing preclinical study as prophylactic and therapeutic treatments for refractory and high-risk adult solid tumor cancers, and as a treatment for relapsed and refractory blood cancers.

About Rose Bengal Disodium

RBD is 4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein disodium, a halogenated xanthene and Provectus’ proprietary lead molecule. Provectus’ current Good Manufacturing Practices (cGMP) RBD is a proprietary pharmaceutical-grade drug substance produced by the Company’s quality-by-design (QbD) manufacturing process to exacting regulatory standards that avoids the formation of uncontrolled impurities currently present in commercial-grade rose bengal. Provectus’ RBD and cGMP RBD manufacturing process are protected by composition of matter and manufacturing patents as well as trade secrets.

An IL formulation (i.e., by direct injection) of cGMP RBD drug substance, cGMP PV-10, is being developed as an autolytic immunotherapy drug product for solid tumor cancers.

IL PV-10 is also undergoing preclinical study for relapsed and refractory pediatric solid tumor cancers, such as neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.5,6

A topical formulation of cGMP RBD drug substance, PH-10, is being developed as a clinical-stage immuno-dermatology drug product for inflammatory dermatoses, such as atopic dermatitis and psoriasis. RBD can modulate multiple interleukin and interferon pathways and key cytokine disease drivers.7

Oral formulations of cGMP RBD are undergoing preclinical study for relapsed and refractory pediatric blood cancers, such as acute lymphocytic leukemia and acute myelomonocytic leukemia.8,9

Oral formulations of cGMP RBD are also undergoing preclinical study as prophylactic and therapeutic treatments for high-risk adult solid tumor cancers, such as head and neck, breast, pancreatic, liver, and colorectal cancers.

Different formulations of cGMP RBD are also undergoing preclinical study as potential treatments for multi-drug resistant (MDR) bacteria, such as Gram-negative bacteria.

Topical formulations of cGMP RBD are also undergoing preclinical study as potential treatments for diseases of the eye, such as infectious keratitis

Tumor Cell Lysosomes as the Seminal Cancer Drug Target

Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. He was awarded the Nobel Prize in 1974 for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Building on the Discovery, Exploration, and Characterization of Lysosomes

Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.10 Cancer progression and metastasis are associated with lysosomal compartment changes11,12, which are closely correlated (among other things) with invasive growth, angiogenesis, and drug resistance13.

RBD selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cells to die. Provectus2,14, external collaborators5, and other researchers15,16,17 have independently shown that RBD triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via RBD: RBD-induced autolytic cell death, or death by self-digestion, in Hepa1-6 murine hepatocellular carcinoma (HCC) cells can be viewed in this Provectus video of the process (ethidium homodimer 1 [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames, with a duration of approximately one hour). Exposure to RBD triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which can be viewed in this Provectus video of the process, with a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators in neuroblastoma cells to show that lysosomes are disrupted upon exposure to RBD.5

Tumor Autolytic Death via RBD: RBD causes acute autolytic destruction of injected tumors (via autolytic cell death), mediating the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens; release of these signaling factors may initiate an immunologic cascade where local response by the innate immune system may facilitate systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Mediated immune signaling pathways may include an effect on STING, which plays an important role in innate immunity.9

Orphan Drug Designations (ODDs)

ODD status has been granted to RBD by the U.S. Food and Drug Administration for metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Intellectual Property

Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which cGMP RBD and related halogenated xanthenes are produced, avoiding the formation of previously unknown impurities that exist in commercial-grade rose bengal in uncontrolled amounts. The requirement to control these impurities is in accordance with International Council on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of RBD and CB (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, 9,839,688, and 10,471,144, with expirations ranging from 2032 to 2035; US patent application numbers include 20200138942 (i.e., 16/678,133), which has been allowed.

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.