On May 29, 2020 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH) reported the presentation of quality of life and certain safety results from the INVICTUS pivotal Phase 3 study evaluating QINLOCK (ripretinib) in adult patients with fourth-line advanced gastrointestinal stromal tumor (GIST) (Press release, Deciphera Pharmaceuticals, MAY 29, 2020, View Source [SID1234558662]). These results were presented as part of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program.

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"The recent FDA approval of QINLOCK marked an important milestone for the entire GIST patient community who had been waiting for a new treatment option designed specifically for their disease," said Matthew Sherman, M.D., Executive Vice President and Chief Medical Officer of Deciphera. "In addition to the impressive efficacy results shown in the INVICTUS Phase 3 study, QINLOCK was shown to have a favorable safety profile. Today’s ASCO (Free ASCO Whitepaper) presentations demonstrate that patients receiving QINLOCK rated their overall health, quality of life, and physical and role function as better than that of patients receiving placebo. These insights into the GIST patient experience are invaluable to us as we establish a new standard of care in this area of unmet medical need."

Quality of Life and Self-Reported Function

In a poster presentation titled, "Quality of life (QoL) and self-reported function with ripretinib in ≥4th-line therapy for patients with gastrointestinal stromal tumors (GIST): Analyses from INVICTUS" (abstract 11535; poster 423), five key measures of quality of life and function were maintained in patients with fourth-line GIST receiving QINLOCK compared with declining measures in patients receiving placebo. Patients in the QINLOCK arm had consistently stable patient reported outcomes (PROs), and the measures suggest these patients were able to maintain quality of life while PROs declined sharply in the placebo arm. Additional highlights from the presentation include:

QINLOCK was associated with an increase in the patients’ self-reported health status on the EuroQol-5D visual analogue scale (EQ-5D-5L VAS) while placebo was associated with a decline (p=0.004).
Patients receiving QINLOCK reported better physical and role functioning on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) compared with a decline observed in patients receiving placebo (p=0.004; p=0.001).
Patients receiving QINLOCK had higher perceptions of their overall health and quality of life compared with patients receiving placebo (both p=0.001).
Differences between treatment arms were clinically significant (using threshold for meaningful change).
Patients receiving QINLOCK reported stable scores on all PRO measures out to cycle 10.
Safety and Impact on Patient Reported Outcomes

In a poster presentation titled, "Safety profile of ripretinib, including impact of alopecia and palmar-plantar erythrodysesthesia syndrome (PPES) on patient reported outcomes (PROs), in ≥4th-line advanced gastrointestinal stromal tumors (GIST): Analyses from INVICTUS" (abstract 11539; poster 427), when stratified by alopecia and PPES, patient-reported assessments of function, overall health, and overall quality of life were shown to be stable. This exploratory analysis demonstrates that alopecia and PPES were not associated with a negative effect on function, overall health, and quality of life. Additional highlights from the presentation include:

For both alopecia and PPES, the majority of the events were of lower severity grades and did not generally worsen over time.
In the QINLOCK arm, grade 1-2 alopecia occurred in 44 patients (52%) and grade 1-2 PPES occurred in 18 patients (21%). No patients experienced grade 3 or higher PPES.
There were no serious adverse events of alopecia or PPES reported.
In the QINLOCK arm, 8.2%, 24%, and 7.1% of patients experienced a treatment-emergent adverse event leading to treatment discontinuation, dose interruption, or dose reduction compared with 12%, 21%, and 2.3% in the placebo arm.
A copy of each presentation is available at www.deciphera.com/science/presentation-publications/.

About QINLOCK (ripretinib)

Indications and Usage

QINLOCK (ripretinib) is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. For more information visit QINLOCK.com.

Important Safety Information

There are no contraindications for QINLOCK.

Palmar-plantar erythrodysesthesia syndrome (PPES): In INVICTUS, Grade 1-2 PPES occurred in 21% of the 85 patients who received QINLOCK. PPES led to dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and dose reduction in 1.2% of patients. Based on severity, withhold QINLOCK and then resume at same or reduced dose.

New Primary Cutaneous Malignancies: In INVICTUS, cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the 85 patients who received QINLOCK with a median time to event of 4.6 months (range 3.8 to 6 months). In the pooled safety population, cuSCC and keratoacanthoma occurred in 7% and 1.9% of 351 patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 patients who received QINLOCK. In the pooled safety population, melanoma occurred in 0.9% of 351 patients. Perform dermatologic evaluations when initiating QINLOCK and routinely during treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Continue QINLOCK at the same dose.

Hypertension: In INVICTUS, Grade 1-3 hypertension occurred in 14% of the 85 patients who received QINLOCK, including Grade 3 hypertension in 7% of patients. Do not initiate QINLOCK in patients with uncontrolled hypertension. Monitor blood pressure as clinically indicated. Based on severity, withhold QINLOCK and then resume at same or reduced dose or permanently discontinue.

Cardiac Dysfunction: In INVICTUS, cardiac failure occurred in 1.2% of the 85 patients who received QINLOCK. In the pooled safety population, cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred in 1.7% of 351 patients, including Grade 3 adverse reactions in 1.1% of patients.

In INVICTUS, Grade 3 decreased ejection fraction occurred in 2.6% of the 77 patients who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram. Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients in the pooled safety population who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram.

In INVICTUS, cardiac dysfunction led to dose discontinuation in 1.2% of the 85 patients who received QINLOCK. The safety of QINLOCK has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or MUGA scan prior to initiating QINLOCK and during treatment, as clinically indicated. Permanently discontinue QINLOCK for Grade 3 or 4 left ventricular systolic dysfunction.

Risk of Impaired Wound Healing: QINLOCK has the potential to adversely affect wound healing. Withhold QINLOCK for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of QINLOCK after resolution of wound healing complications has not been established.

Embryo-Fetal Toxicity: QINLOCK can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 week after the final dose. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 1 week after the final dose. QINLOCK may impair fertility in males of reproductive potential.

Adverse Reactions: The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.

The safety and effectiveness of QINLOCK in pediatric patients have not been established.

Administer strong CYP3A inhibitors with caution. Monitor patients who are administered strong CYP3A inhibitors more frequently for adverse reactions. Avoid concomitant use with strong CYP3A inducers.

Please click here to see the full Prescribing Information for QINLOCK.

About the INVICTUS Phase 3 Study

INVICTUS is a Phase 3 randomized, double-blind, placebo-controlled, international, multicenter clinical study evaluating the safety, tolerability, and efficacy of QINLOCK compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. Patients were randomized 2:1 to either 150 mg of QINLOCK or placebo once daily. The primary efficacy endpoint is progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). The median PFS in the study was 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, p<0.0001). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR) and Overall Survival (OS). QINLOCK demonstrated an ORR of 9.4% compared with 0% for placebo (p =0.0504). QINLOCK also demonstrated a median OS of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).

On May 29, 2020 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported updated data from the dose escalation portion of the company’s Phase 1/2 clinical trial of ARV-110 in men with metastatic castration-resistant prostate cancer (mCRPC), to be shared as an oral presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on May 29, 2020 (Press release, Arvinas, MAY 29, 2020, View Source [SID1234558660]). ARV-110 is a potent, selective, orally available androgen receptor (AR) degrader, and the ASCO (Free ASCO Whitepaper) presentation highlights promising clinical activity, including both efficacy and AR degradation, in a heavily pretreated patient population. ­

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"For ARV-110 to show signs of efficacy in these patients at this early stage of development is strong validation of our PROTAC technology," said John Houston, Ph.D., President and Chief Executive Officer at Arvinas. "In addition, seeing AR degradation demonstrates that ARV-110 is acting on-mechanism to achieve this result, and we are excited to continue clinical development in the hope of bringing a new therapeutic option to patients with significant unmet need."

"The responses we see are the first powerful examples in patients of the potential benefits of protein degradation pharmacology compared to classic inhibition or antagonism, which failed in these patients while degradation showed clinical benefit," added Ron Peck, M.D., Chief Medical Officer at Arvinas. "This is a patient population where other therapies would be expected to have little to no benefit, and we are very pleased with the early clinical efficacy data and safety profile we are seeing and think it bodes well for both ARV-110 and the PROTAC platform."

The dose escalation portion of Arvinas’ Phase 1/2 clinical trial of ARV-110 is designed to assess safety, tolerability, and pharmacokinetics (PK) in men with mCRPC who have progressed on standard of care therapies, as well as to identify a recommended Phase 2 dose. To date, ARV-110 has shown a favorable safety profile, and PK have been generally dose proportional, reaching exposures associated with tumor inhibition in preclinical models at 140 mg. In the data released today, Arvinas also shared evidence of in-tumor AR reduction, the first demonstration of successful targeted protein degradation by a PROTAC protein degrader in humans.

ARV-110 has demonstrated evidence of activity at doses and in AR mutational backgrounds in which responses would be expected based on preclinical data. As of the April 20, 2020 data cut-off, 20 patients were evaluable for prostate-specific antigen (PSA) response, including 12 patients treated at 140 mg or higher (these 12 patients exclude one patient who received two weeks of therapy prior to discontinuing due to a rosuvastatin-related dose limiting toxicity).

Of those 12 patients treated at 140 mg and above, circulating tumor DNA (ctDNA) analysis of five patients showed AR forms not degradable by ARV-110 in preclinical studies (i.e., L702H point mutations and AR-V7 splice variants). In the group of seven remaining patients who had forms of AR degradable by ARV-110 (other AR point mutations, AR amplification, and wildtype AR), two patients achieved confirmed PSA responses that remain ongoing with additional follow-up since the abstract was submitted.

One of these patients had a 74% decline from baseline in PSA and remained without progression after 30 weeks, as of the data cut-off. This patient did not have measurable disease at baseline for assessment by Response Evaluation Criteria in Solid Tumors (RECIST). The second patient had both a deep PSA response (97% decline from baseline) and a confirmed RECIST response (80% decrease from baseline in tumor mass) and remains without progression after 18 weeks. Both responses, which were in patients at the 140 mg dose, were achieved by ARV-110 despite prior enzalutamide, abiraterone, chemotherapy, and other therapies. Tumors from both patients have H875Y and T878A point mutations in AR, which are known to drive resistance to current standard of care treatments and have been degraded by ARV-110 in preclinical studies. In addition to these two patients, PSA reductions were observed in other patients but did not meet a 50% reduction in PSA threshold at data cutoff, and four patients remain on ARV-110 without radiographic progression for at least 20 weeks.

A potential drug-drug interaction between ARV-110 and rosuvastatin (ROS) was identified during the trial. Of the 22 patients enrolled, two had concurrent use of ROS. One patient receiving 280 mg ARV-110 experienced a Grade 4 dose-limiting toxicity (DLT) of elevated aspartate transaminase/alanine transaminase (AST/ALT) followed by acute renal failure. The second patient, receiving 70 mg ARV-110, experienced a Grade 3 AST/ALT elevation, which resolved after the removal of ROS, and the patient was retreated with ARV-110. Follow-up exploratory findings indicate that ROS concentrations were elevated in both patients who had liver function test (LFT) increases. Subsequent in vitro transport pump studies indicate that ARV-110 inhibits breast cancer resistant pump (BCRP) transporter, of which ROS is a substrate. Following the initial data that supported a potential interaction with ROS, concomitant use of ROS was precluded, and no other related Grade 3 or 4 adverse events have since been reported. Six other patients have received concomitant non-ROS statins without AST/ALT adverse events.

Dose escalation and enrollment continues, with the most recent cohort initiating dosing in May 2020 at 420 mg. The expansion portion of the Phase 1/2 trial is expected to begin once the recommended Phase 2 dose has been determined and will evaluate the anti-tumor activity of ARV-110 through assessment of PSA response, using the Prostate Cancer Working Group 3 Criteria, and overall RECIST response rate in patients with measurable disease. The expansion will further investigate a link between AR genomic profile and efficacy, which could inform an enrichment strategy. Arvinas plans to provide updated information on the ARV-110 Phase 1/2 study by the end of 2020.

Arvinas Webcast Investor Meeting
The company will host a conference call and webcast at 8:30 AM ET today to discuss these data. Participants are invited to listen by dialing (844) 467-7654 (domestic) or (602) 563-8497 (international) five minutes prior to the start of the call and providing the passcode access code 8069179. A listen-only webcast of the conference call can also be accessed through the "Investors + Media" tab on the Arvinas website, www.arvinas.com, and a replay will be available for six weeks following the call.

About ARV-110
ARV-110 is an orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About Metastatic Castration-Resistant Prostate Cancer (mCRPC)

In the United States, prostate cancer is both the second most prevalent cancer in men and the second leading cause of cancer death in men. The American Cancer Society predicts that one in nine men will be diagnosed with prostate cancer in his lifetime. Metastatic castration-resistant prostate cancer (mCRPC) is defined by disease progression despite androgen deprivation therapy and is often correlated with rising levels of prostate-specific antigen (PSA).

Current AR-targeted standard of care treatments for mCRPC are less effective in patients whose disease has increased levels of androgen production, AR gene or gene enhancer amplification, or AR point mutations. Up to 25 percent of patients do not respond to second-generation hormone therapies like abiraterone and enzalutamide, and the vast majority of responsive patients will ultimately become resistant, resulting in poor prognoses for men diagnosed with this devastating condition.

On May 29, 2020 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that the Japan Ministry of Health, Labour and Welfare (MHLW) has approved XTANDI (enzalutamide), an oral androgen receptor signaling inhibitor, for the treatment of prostate cancer patients with distant metastasis. With this approval, XTANDI is now indicated for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC), a form of prostate cancer that has spread to other parts of the body and still responds to a medical or surgical treatment that lowers testosterone (Press release, Astellas, MAY 29, 2020, View Source [SID1234558658]).1,2 This is in addition to an existing indication for castration-resistant prostate cancer (CRPC).

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The approval for mHSPC is based on results from the ARCHES triali, a randomized multi-national Phase 3 study which evaluated enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT in 1,150 men with mHSPC and met its primary endpoint of radiographic progression-free survival (rPFS).3 It is also supported by data from the ENZAMET trialii, an overseas Phase 3 study evaluating enzalutamide plus ADT versus ADT plus a standard nonsteroidal antiandrogen therapy (bicalutamide, nilutamide or flutamide) in men with mHSPC.4

"Enzalutamide with androgen deprivation therapy led to a significant delay in the risk of progression of metastatic disease or death, and this delay was associated with maintained quality of life and a reduced need for subsequent therapies over time. These endpoints are all critically important to men with metastatic prostate cancer," said Andrew Armstrong, M.D., Professor of Medicine, Surgery, Pharmacology and Cancer Biology, Director of Research in the Duke Cancer Institute’s Center for Prostate and Urologic Cancers and lead investigator of the ARCHES trial. "The research supporting the approval provides compelling evidence to consider enzalutamide as a treatment option for men with mHSPC."

Data from the ARCHES trial showed enzalutamide plus ADT significantly reduced the risk of radiographic progression or death by 61% versus placebo plus ADT in men with mHSPC.5 The ENZAMET trial demonstrated a 33% reduction in the risk of death in men with mHSPC receiving enzalutamide plus ADT compared to those who took a nonsteroidal antiandrogen therapy plus ADT.6

The safety analyses of the ARCHES and ENZAMET trials were generally consistent with the safety profile of enzalutamide in previous clinical trials in CRPC. In the ARCHES trial, adverse drug reactions were reported in 53.0% of patients. Major adverse drug reactions with an incidence of more than 10% were hot flush (20.5%) and fatigue (14.9%). In the ENZAMET trial, serious adverse drug reactions were reported in 3.0% of patients. Serious adverse drug reactions observed in 2 or more patients were seizure (0.9%), hypertension (0.5%) and fatigue (0.4%).

"Today’s MHLW approval of XTANDI marks continued progress to provide a treatment option to men earlier in their advanced prostate cancer treatment journey," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development. "At Astellas, we have made a commitment to fight cancer and continue to build a robust oncology portfolio to help meet the needs of patients."

About metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
In men with prostate cancer, the disease is considered metastatic once the cancer has spread outside of the prostate gland to other parts of the body. Men are considered hormone- (or castration-) sensitive if their disease still responds to medical or surgical treatment that lowers testosterone.

About the ARCHES trial
The company-sponsored, Phase 3, randomized, multinational, double-blind, placebo-controlled, ARCHES trial (NCT02677896) enrolled 1,150 patients with mHSPC at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. Patients in the trial were randomized to receive enzalutamide 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy. The primary endpoint of the trial was radiographic progression-free survival (rPFS) assessed by blinded independent central review. rPFS was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation. Patients were stratified by volume of disease (low vs high) and prior docetaxel therapy for prostate cancer (no prior docetaxel, 1-5 cycles, or 6 prior cycles).3

About the ENZAMET trial
ENZAMET is an overseas Phase 3 study funded by Astellas and sponsored by the University of Sydney with trial sites in Australia, Canada, Ireland, New Zealand, UK and U.S. The trial evaluated the potential of enzalutamide plus androgen deprivation therapy (ADT) versus a conventional non-steroidal anti androgen (NSAA) plus ADT in 1,125 men with mHSPC. The primary endpoint for the trial is overall survival (OS; 3-years). Additional details about ENZAMET (NCT02446405) are available on www.clinicaltrials.gov.4

About XTANDI (enzalutamide)
Enzalutamide is an androgen receptor signaling inhibitor indicated for the treatment of patients with castration-resistant prostate cancer (CRPC) and metastatic hormone-sensitive prostate cancer (mHSPC).

Important Safety Information
For important Safety Information for enzalutamide please see the Package Insert.

On May 29, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that the New Drug Application ("NDA") for savolitinib for the treatment of non-small cell lung cancer ("NSCLC") with MET Exon 14 skipping mutations has been accepted for review by the China National Medical Products Administration (NMPA) (Press release, Hutchison China MediTech, MAY 29, 2020, https://www.chi-med.com/savolitinib-china-nda-acceptance-for-nsclc-with-met-exon-14-skipping/ [SID1234558657]).

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The NDA is supported by data from an open-label, Phase II registration study. Interim data were presented on the first 50 treated patients at the Chinese Society of Clinical Oncology Annual Meeting in September 2019. An updated analysis with 70 patients in the study will be presented by Professor Shun Lu as part of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") 2020 Virtual Scientific Meeting, available on May 29, 2020 at 8:00 a.m. Eastern Time ("Phase II Study of Savolitinib in Patients with Pulmonary Sarcomatoid Carcinoma and Other Types of Non-Small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutations", abstract #9519).

"With today’s NDA acceptance, savolitinib is one step closer to benefitting a specific group of NSCLC patients who have limited treatment options today and we are very proud of that. After many years of collaboration with AstraZeneca, we hope that this NDA is the first of many globally for savolitinib." Mr Christian Hogg, Chief Executive Officer of Chi-Med, commented.

It is estimated that 2-3% of NSCLC patients have MET Exon 14 skipping mutations, which predicts poor prognosis.[i] Annual incidence of lung cancer in China accounted for 37.0% of the world’s annual incidence of lung cancer in 2018.[ii]

In 2011, Chi-Med entered into a global licensing and joint development and commercialization agreement with AstraZeneca (LSE, STO, NYSE: AZN) for savolitinib. Savolitinib’s global development plan includes NSCLC and kidney cancer, and additional MET-driven tumors are being explored.

About Savolitinib
Savolitinib is a small molecule inhibitor of MET, a receptor tyrosine kinase enzyme which has been shown to function abnormally in many types of solid tumors. It was developed as a potent and highly selective oral inhibitor. In clinical studies to date, involving over 1,000 patients, savolitinib has shown promising clinical efficacy in patients with MET gene alterations in multiple tumor types with an acceptable safety profile.

Savolitinib in NSCLC:
Phase II in MET Exon 14 deletion NSCLC (NCT02897479) – NDA accepted and data to be presented at ASCO (Free ASCO Whitepaper) 2020.

SAVANNAH Phase II study of savolitinib in combination with Tagrisso in patients who have progressed following Tagrisso due to MET amplification (NCT03778229) – The SAVANNAH study is a single-arm, open-label study in epidermal growth factor receptor (EGFR) mutation positive NSCLC patients following first- or second-line Tagrisso therapy.

Savolitinib in kidney cancer:
CALYPSO Phase II of savolitinib in combination with Imfinzi PD-L1 inhibitor in renal cell carcinoma ("RCC") (NCT02819596) – The CALYPSO study is an investigator initiated open-label Phase I/II study of savolitinib in combination with Imfinzi, an anti-PD-L1 antibody owned by AstraZeneca. The study is evaluating the safety and efficacy of the savolitinib/Imfinzi combination in patients with papillary RCC ("PRCC") and clear cell RCC.

SAVOIR Phase III in MET-positive PRCC (NCT03091192) – In December 2018, enrollment was terminated in SAVOIR, a global Phase III registration study of savolitinib monotherapy compared with sunitinib monotherapy in MET-positive PRCC. The early termination was driven by factors external to the SAVOIR study. Data from the approximately 60 patients randomized in SAVOIR prior to termination matured during 2019 and will be presented by Professor Toni K. Choueiri at ASCO (Free ASCO Whitepaper) 2020 Virtual Scientific meeting in an oral abstract session, available on May 29, 2020 at 8:00 a.m. Eastern Time ("SAVOIR: A Phase III Study of Savolitinib Versus Sunitinib in Patients with MET-driven Papillary Renal Cell Carcinoma", abstract #5002). Based on these data, AstraZeneca and Chi-Med are actively evaluating the opportunity to restart clinical work in PRCC for monotherapy savolitinib.

Savolitinib in other cancer indications:
Investigator-initiated studies of savolitinib have been undertaken in gastric cancer, prostate cancer and colorectal cancer.

On May 29, 2020 Achilles Therapeutics ("Achilles"), a clinical stage biopharmaceutical company developing personalised cancer immunotherapies, reported that it has dosed the first patient in a Phase I/II study of a clonal neoantigen T cell (cNeT) therapy in patients with recurrent or metastatic malignant melanoma (Press release, Achilles Therapeutics, MAY 29, 2020, View Source [SID1234558656]). This is the first tumour-infiltrating lymphocyte (TIL) therapy to enter clinical trials where the TILs have been specifically selected to target clonal neoantigens – antigens which are believed to be present on all tumour cells.

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The THETIS study is an open-label, multi-centre Phase I/II trial evaluating the safety, tolerability and clinical efficacy of cNeT therapy as a single dose in patients with recurrent or metastatic malignant melanoma. The trial is expected to recruit approximately 20 patients and report initial data in the first half of 2021. Recruitment is ongoing across sites in the UK, with additional sites to open in the US and Europe. Link to Study.

"The dosing of our first melanoma patient with a cell therapy to specifically target all cancer cells, marks a significant milestone in delivering the first precision TIL therapy. We have used a unique and proprietary data set derived from cancer patients over a period of many years (TRACERx) to generate a powerful predictive tool which, together with the DNA of a patient’s own tumour, can be used to create an entirely personalised cell therapy designed to be exquisitely specific and effective," said Dr Iraj Ali, CEO of Achilles Therapeutics. "As we continue to navigate the unprecedented COVID-19 pandemic, we are incredibly grateful to patients and their families, investigators and their colleagues at clinical study sites, and our employees for working to advance this important study that has the potential to treat a very challenging and life-threatening cancer."

"Patients with metastatic melanoma have very limited treatment options after immune checkpoint inhibitors have failed," said Professor Ruth Plummer, Clinical Professor of Experimental Cancer Medicine, Faculty of Medical Sciences, Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation. "This is the first patient in the UK to receive a personalised clonal neoantigen reactive T cell product and we are very excited that this has been achieved in Newcastle in the midst of such unprecedented times, and is testament to the great collaboration between us and Achilles."

Achilles is developing personalised T cell therapies for solid tumours targeting clonal neoantigens: protein markers unique to each patient that are present on the surface of all cancer cells. Using its PELEUS bioinformatics platform, Achilles can identify clonal neoantigens from each patient’s unique tumour profile which are present on every cancer cell. Achilles uses its proprietary process to manufacture T cells (cNeT) which exquisitely target a specific set of clonal neoantigens in each patient. Targeting multiple clonal neoantigens that are present on all cancer cells, but not on healthy cells, reduces the risk that new mutations can induce immune evasion and therapeutic resistance, and allows individualised treatments to target and destroy tumours without harming healthy tissue.