On September 30, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage immuno-oncology company, reported preliminary results from its ongoing Phase 2 basket trial, evaluating DPX-Survivac in combination with Merck’s Keytruda (pembrolizumab) and intermittent low dose cyclophosphamide (CPA) in patients with advanced and metastatic solid tumors (Press release, IMV, SEP 30, 2019, View Source [SID1234539946]). The data were presented during the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress, being held September 27 – October 1, 2019, in Barcelona, Spain.

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"We are encouraged by the initial response observed from these preliminary data, which feature a safety profile consistent with observations across other studies of DPX-Survivac as well as promising signs of clinical activity. Importantly, these results expand our clinical dataset into four additional hard-to-treat solid tumor indications, as we continue to explore the broad potential of our targeted T cell therapy in more than 20 solid and hematological tumor types that express survivin," said Frederic Ors, IMV’s Chief Executive Officer. "Later this year, we anticipate additional data from ongoing studies of DPX-Survivac in our lead indications – including topline results from DeCidE1, a Phase 2 study evaluating DPX-Survivac in ovarian cancer, and updated results from SPiRel, a Phase 2 study evaluating DPX-Survivac in combination with Keytruda in r/r DLBCL – both of which have demonstrated this program’s potential to safely generate a durable clinical response."

Preliminary Results from the Phase 2 Basket Trial

At the time of cut-off, 23 patients were enrolled across all five patient cohorts. This includes 19 patients across all cohorts who received DPX-Survivac in combination with pembrolizumab with CPA, and four patients from the ovarian cancer cohort receiving DPX-Survivac with only pembrolizumab:

Preliminary results from the first on-study scan showed tumor reduction in patients with ovarian cancer (with and without CPA), non-small cell lung cancer (NSCLC) and bladder cancer;
Partial responses observed at first scan in two subjects (bladder cancer, ovarian cancer); 19/23 subjects are still active on study treatment.
T cell infiltration observed in biopsy samples from subjects who achieved tumor reduction on treatment;
Eight ovarian cancer patients were enrolled in the study, randomized 1:1 to treatment with and without CPA. Tumor control and tumor reductions were observed in both groups; and
Safety evaluation on all evaluable patients demonstrated that treatment was well-tolerated, with no related Grade 3-4 or immune-related adverse events (AEs) reported.
The poster is available on the Investors section of the company’s website, under "Events, Webcasts & Presentations" at www.imv-inc.com.

About the Phase 2 Basket Trial

IMV’s Phase 2 basket trial is an open label, multi-center study, evaluating DPX-Survivac across five cohorts of patients with bladder cancer, liver cancer (hepatocellular carcinoma), ovarian cancer (with and without CPA), NSCLC and tumors shown to be positive for the microsatellite instability high (MSI-H) biomarker.

Subjects will receive DPX-Survivac (SC: 2 x 0.25 mL every three weeks, followed by up to 11 x 0.1 mL every nine weeks), in combination with pembrolizumab (IV: 200 mg every 3 weeks cycle) and CPA (oral: 50 mg BID on alternating weeks) across five cohorts of patients with bladder cancer, liver cancer (hepatocellular carcinoma), ovarian cancer, NSCLC and tumors shown to be positive for the microsatellite instability high (MSI-H) biomarker. The study is designed to assess primary endpoints of safety and objective response rate (ORR), with multiple secondary and exploratory measures.

The study included a safety lead-in, which included 20 patients from all five cohorts. The five cohorts are now expanded to recruit additional subjects following a Simon two stage design. Enrollment in the ovarian cancer cohort will be randomized 1:1 into two arms with and without CPA. All other cohorts will utilize a single-arm design and administer treatment with the triple combination. As of Sept. 27th, 2019, 28 patients are enrolled (50 were screened). IMV expects to enroll 184 patients across clinical sites in the U.S. and Canada.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapies that programs targeted T cells in vivo. It has demonstrated the potential for industry-leading targeted, persistent, and durable T cell activation. IMV believes this mechanism of action (MOA) is key to generating durable solid tumor regressions. DPX-Survivac consists of survivin-based peptides formulated in IMV’s proprietary DPX drug delivery platform. DPX-Survivac is designed to work by eliciting a cytotoxic T cell immune response against cancer cells presenting survivin peptides on their surface.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to chemotheratherapies. IMV has identified over 20 cancer indications in which survivin can be targeted by DPX-Survivac.

DPX-Survivac has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer, as well as orphan drug designation status from the U.S. FDA and the European Medicines Agency (EMA) in the ovarian cancer indication.

On September 30, 2019 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a clinical-stage biopharmaceutical company focused on the development of novel therapeutics for the treatment of rare diseases, reported positive results from the Phase 2a portion of its open-label Phase 1/2 clinical trial of mavorixafor (X4P-001) in combination with axitinib (Inlyta) in patients with advanced clear cell renal cell carcinoma (ccRCC) (Press release, X4 Pharmaceuticals, SEP 30, 2019, View Source [SID1234539945]). Data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress today in Barcelona.

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Combination therapy with mavorixafor and approved tyrosine kinase inhibitor (TKI) axitinib was generally well tolerated with a manageable safety profile and demonstrated clinical improvement with encouraging median progression free survival (mPFS) in a heavily pretreated advanced ccRCC patient population. Of the 65 patients in the trial, 49 patients (or 75%) received mavorixafor + axitinib as a third- to ninth-line therapy, having received between two and eight prior therapies with a TKI, immuno-oncology (IO) agent, or other systemic therapy. Fifty-seven of the 65 patients in the trial (or 88%) had an intermediate or poor prognosis.

Overall mPFS across clinically evaluable patients receiving mavorixafor + axitinib (n=62) was 7.4 months. Predefined subpopulations examined patients with immediate prior TKI and IO treatment. Patients treated in the subgroup with immediate prior TKI therapy (n=34) demonstrated an objective response rate (ORR) of 18% and an increased mPFS of 7.4 months. This is a greater than 50% improvement from the 4.8-month historical mPFS with axitinib alone.1 Patients treated with mavorixafor + axitinib in the subgroup with immediate prior IO therapy (n=18) had an ORR of 61% and an increased mPFS of 11.6 months. In addition, eight of the 65 patients remain on the combination therapy today, with durations of treatment of 17 months or longer. Results suggest mavorixafor may enhance clinical response to axitinib and other TKIs that target tumor angiogenesis, as well as immunotherapy agents.

"In recent years a growing number of vascular endothelial growth factor (VEGF) TKI-based therapies (e.g., axitinib + pembrolizumab), have improved outcomes for patients with ccRCC. Despite these advances, most patients eventually develop resistance to therapy, and new treatment options are necessary to meet this unmet medical need," commented David F. McDermott, M.D., Beth Israel Deaconess Medical Center, Harvard Medical School and lead investigator of the study. "In this trial of mavorixafor, a novel CXCR4 pathway inhibitor, and axitinib in patients with metastatic ccRCC who had failed prior therapy, the combination was well tolerated and the anti-tumor activity was encouraging. We look forward to confirming the efficacy of mavorixafor in a randomized trial."

This Phase 1/2, multi-center, open-label trial of mavorixafor in combination with axitinib included 65 patients with histologically confirmed advanced ccRCC, all of whom received at least one prior systemic therapy. The safety analyses included 65 patients from Phases 1/2 who were treated with 400 mg mavorixafor (200 mg twice daily or 400 mg once daily) + 5 mg axitinib twice daily. Treatment responses were assessed using Response Evaluation Criteria in Solid Tumor, or RECIST v1.1 (a validated set of criteria to assess changes in tumor burden), every eight weeks from day one for 80 weeks, and then every 12 weeks thereafter, by blinded, independent central review. Treatment-related serious adverse events were diarrhea, hyperkalemia and hypertension (n=2, or 3%) and blood creatinine increased, dehydration, fatigue, hepatic enzyme increase, nausea, sepsis, trachea-oesophageal fistula, and vomiting (n=1 each, or 1.5%).

"These promising results, especially among heavily pre-treated patients with poor prognoses, add to a published body of evidence supporting mavorixafor’s generally favorable safety and tolerability profile and its novel CXCR4 mechanism of action that has been shown to induce immune-mediated antitumor activity as a single agent and in combination with approved therapies," said Lynne Kelley, M.D., FACS, Chief Medical Officer of X4 Pharmaceuticals. "We are encouraged by these data, including the eight patients who remain on combination therapy with mavorixafor and axitinib for 17 months or longer. We look forward to continuing to explore the potential benefit of mavorixafor in underserved cancer patients with solid tumors, including as a potential triple combination agent in addition to TKI and checkpoint inhibitor therapies or in combination with other standard of care treatments."

Mavorixafor is a potentially first-in-class, once-daily, oral, small molecule antagonist of chemokine receptor CXCR4. CXCR4 signaling is thought to contribute to the lack or loss of tumor responsiveness to angiogenesis inhibitors, like axitinib. Elevated expression of CXCR4 by RCC tumors is also correlated with an overall poor prognosis. In xenograft models studied previously, mavorixafor in combination with axitinib, a VEGF receptor TKI, reduced myeloid-derived suppressor cell infiltration and proangiogenic signals, and demonstrated greater than additive antitumor activity.

Details of the investor conference call and webcast are as follows:
Time and Date: Monday, September 30 at 8:00 AM EDT / 2:00 PM CEST
US Toll-Free Dial-In Number: (866) 721-7655
International Dial-In Number: (409) 216-0009 / Spain 0934923253
Conference ID: 4787329
Webcast: A live audio webcast of the conference call may be accessed in the "Investors" section of the Company’s website at the following link: View Source

About Mavorixafor

X4 Pharmaceuticals’ lead product candidate, mavorixafor (X4P-001), is a potentially first-in-class, once-daily, oral inhibitor of CXCR4, currently in Phase 2 development for the treatment of clear cell renal cell carcinoma (ccRCC). Mavorixafor has demonstrated single and combination agent activity and proof of mechanism in Phase 1b and Phase 2a trials, respectively, along with a favorable safety and tolerability profile. Mavorixafor is also in development for the treatment of WHIM syndrome, as well as Severe Congenital Neutropenia (SCN) and Waldenström’s macroglobulinemia (WM). Mavorixafor was designated orphan drug status by the U.S. Food and Drug Administration in 2018 and by the European Commission in 2019 for the treatment of WHIM syndrome.

On September 30, 2019 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive results from the Phase III IMvigor130 study evaluating Tecentriq (atezolizumab) plus platinum-based chemotherapy versus chemotherapy alone for the first-line (initial) treatment of people with previously untreated locally advanced or metastatic urothelial carcinoma (mUC) eligible and ineligible for cisplatin chemotherapy (Press release, Genentech, SEP 30, 2019, View Source [SID1234539943]). In the study, Tecentriq plus chemotherapy showed a statistically significant improvement in progression-free survival (PFS) compared with platinum-based chemotherapy alone (median PFS=8.2 versus 6.3 months; hazard ratio [HR]=0.82, 95% CI: 0.70-0.96; p=0.007). Encouraging overall survival (OS) results were observed for Tecentriq plus chemotherapy compared with chemotherapy alone in the intention-to-treat (ITT) population, however these data did not reach statistical significance at this interim analysis (median OS=16.0 versus 13.4 months; HR=0.83, 95% CI: 0.69-1.00). Safety in the Tecentriq plus chemotherapy arm appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination.

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"We are pleased with these positive results from the IMvigor130 study, which show Tecentriq plus chemotherapy may provide a meaningful benefit for people newly diagnosed with advanced bladder cancer," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "There remains a high unmet need for people with advanced bladder cancer, where chemotherapy alone is the current standard of care. These results reinforce the role of immunotherapy in treating this aggressive disease."

Additional data from the Tecentriq monotherapy arm were also presented in the ITT population and people with different levels of PD-L1 expression. Encouraging OS results were observed with Tecentriq monotherapy in people with high PD-L1 expression (IC2/3), however these data were not formally tested per the hierarchical design of the trial. Follow-up will continue until the next analysis.

These data will be presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress Presidential Symposium from 5:53 – 6:05 p.m. CEST (Abstract LBA14) and were featured in the official ESMO (Free ESMO Whitepaper) press program.

Tecentriq was the first cancer immunotherapy approved in advanced bladder cancer. Tecentriq has accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adults with locally advanced or mUC, including those who are not eligible for cisplatin-containing chemotherapy and whose tumors express high levels of PD-L1 (PD-L1–stained tumor-infiltrating immune cells covering ≥5% of the tumor area) as determined by an FDA-approved test or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. The accelerated approval also includes the treatment of adults with locally advanced or mUC whose disease had progressed during or following platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). These accelerated approvals are based on tumor response rate and durability of response. Continued approval in these types of bladder cancer may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Currently, there are four ongoing Phase III studies evaluating Tecentriq alone and in combination with other medicines in early and advanced bladder cancer. Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies, across lung, genitourinary, skin, breast, gastrointestinal, gynecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMvigor130 study

IMvigor130 is a multicenter, partially blinded, randomized Phase III study, evaluating the efficacy and safety of Tecentriq in combination with chemotherapy or alone versus chemotherapy alone for people with mUC who have not received prior systemic therapy for metastatic disease. It enrolled 1,213 people who received:

Tecentriq plus platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin), or
Tecentriq, or
Platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin) plus placebo (control arm).
In the Tecentriq combination arm, the co-primary endpoints are OS and PFS as assessed by investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The secondary endpoints are objective response rate and duration of response, as assessed by investigator using RECIST v1.1, and independent review facility-assessed PFS.

A summary of the key study results is included below:

Tecentriq + platinum-based chemotherapy

n=451

Placebo + platinum-based chemotherapy

n=400

PFS (co-primary endpoint)

Median PFS (months)

(95% CI)

8.2

(6.5, 8.3)

6.3

(6.2, 7.0)

HR (95% CI)

0.82 (0.70, 0.96)

P value

P=0.007

OS (co-primary endpoint)

Median OS (months)

16.0

13.4

(95% CI)

(13.9, 18.9)

(12.0, 15.2)

HR (95% CI)

0.83 (0.69, 1.00)*

ORR (secondary endpoint)

Responders (%)

212 (47.4%)

174 (43.8%)

95% CI

(42.7%, 52.2%)

(38.9%, 48.9%)

Complete response %

56 (12.5%)

27 (6.8%)

*The OS result did not cross the pre-specified efficacy boundary for statistical significance. Follow-up will continue until the next interim analysis.

Safety for the Tecentriq plus chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. There appeared to be no worsening of tolerability with the addition of Tecentriq to chemotherapy compared with chemotherapy alone. All cause Grade 3-4 adverse events (AEs) were reported in 85% of people receiving Tecentriq plus chemotherapy compared with 86% of people receiving chemotherapy alone. Treatment-related Grade 3-4 AEs were reported in 83% of people receiving Tecentriq plus chemotherapy compared with 81% of people receiving chemotherapy alone. Any grade AEs leading to any treatment discontinuation of Tecentriq or placebo were observed in 11% and 7% of people in the combination arm compared with the chemotherapy arm respectively.

About bladder cancer

According to the American Cancer Society (ACS), it is estimated that more than 80,000 Americans will be diagnosed with bladder cancer in 2019, and about 11% of new diagnoses are made when bladder cancer is in advanced stages. There is a dramatic difference in survival rates between early and advanced bladder cancer. The ACS estimates that approximately 90% of people will live five or more years when diagnosed with the earliest stage of the disease, compared to 40% when diagnosed in advanced stages (stage III-IV) of the disease. Men are about three to four times more likely to get bladder cancer during their lifetime than women.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Tecentriq U.S. Indications

Tecentriq is a prescription medicine used to treat adults with:

A type of bladder and urinary tract cancer called urothelial carcinoma. Tecentriq may be used when your bladder cancer:

has spread or cannot be removed by surgery, and if you have any one of the following conditions:
you are not able to take chemotherapy that contains a medicine called cisplatin, and your doctor has tested your cancer and found high levels of a specific protein on your cancer called programmed death-ligand 1 (PD-L1), or
you are not able to take chemotherapy that contains any platinum regardless of the levels of "PD-L1" status, or
you have tried chemotherapy that contains platinum, and it did not work or is no longer working
The approval of Tecentriq in these patients is based on a study that measured response rate and duration of response. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

It is not known if Tecentriq is safe and effective in children.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

Lung problems (pneumonitis)–signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain
Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
Intestinal problems (colitis)–signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucus in your stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary)–signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, the voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
Problems in other organs–signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
Severe infections–signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
Severe infusion reactions–signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of your face or lips, dizziness, fever, feeling like passing out, and back or neck pain
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
are pregnant or plan to become pregnant. Tecentriq can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
A healthcare provider should do a pregnancy test before they start treatment with Tecentriq.
They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq.
are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into the breast milk. Patients should not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

feeling tired or weak
nausea
constipation
cough
shortness of breath
decreased appetite
Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or View Source

Report side effects to Genentech at 1-888-835-2555.

Please visit View Source for the Tecentriq full Prescribing Information for additional Important Safety Information.

About Genentech in personalized cancer immunotherapy

For more than 30 years, Genentech has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer. The goal of PCI is to provide each person with a treatment tailored to harness his or her own immune system to fight cancer. Genentech is studying more than 10 cancer immunotherapy medicines across 70 clinical trials alone or in combination with other medicines. In every study we are evaluating biomarkers to identify which people may be appropriate candidates for our medicines. For more information visit View Source

On September 30, 2019 Genomic Health, Inc. (NASDAQ: GHDX) reported results from a new analysis of the Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, which reinforce the unique value of the Oncotype DX Breast Recurrence Score test to guide the use of adjuvant chemotherapy for women with hormone receptor-positive (HR+), HER2-negative, early-stage breast cancer and identify those patients who derive a significant benefit from treatment (Press release, Genomic Health, SEP 30, 2019, View Source [SID1234539942]). The findings, published today in JAMA Oncology1 and presented at the ESMO (Free ESMO Whitepaper) 2019 Congress2, are consistent with results from the B20 trial3 and show that, in patients with high Recurrence Score results (26-100) treated with endocrine therapy plus chemotherapy, outcomes were better compared to what would be expected with endocrine therapy alone. The analysis also provides details on the outcomes of different chemotherapy regimens for the minority of patients who benefit from chemotherapy.

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"We’re pleased to see that the landmark TAILORx trial continues to receive global recognition, as evidenced by this fourth peer-reviewed publication," said Steven Shak, M.D., chief scientific officer, Genomic Health. "TAILORx established that the Oncotype DX test definitively identifies the vast majority of women with early-stage breast cancer who receive no benefit from chemotherapy and the important minority for whom chemotherapy can be life-saving. The additional insight from this new analysis is consistent with, and further supports, the conclusion that the Recurrence Score predicts which patients benefit from chemotherapy and which patients do not, giving them the standard of care they deserve."

The objective of this secondary analysis of TAILORx, the largest ever breast cancer treatment trial, sponsored by the National Cancer Institute (NCI) and led by the ECOG-ACRIN Cancer Research Group, was to evaluate clinical outcomes for patients with a high Recurrence Score result assigned to receive adjuvant chemotherapy plus endocrine therapy. In this group of 1,389 women, treated largely with standard of care taxane and/or anthracycline-containing adjuvant chemotherapy regimens, the estimated proportion free from distant recurrence at five years was about 93%, an outcome much better than expected with endocrine therapy alone in this population.

"Last year, TAILORx established the highest level of evidence and unprecedented precision supporting the use of the Oncotype DX Breast Recurrence Score test to guide adjuvant chemotherapy treatment for women with early-stage breast cancer," said lead author Joseph A. Sparano, M.D., associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice chair of the ECOG-ACRIN Cancer Research Group. "This new analysis provides the largest dataset on outcomes in patients with high Recurrence Score results, and confirms the importance of using the test to identify the patients who will receive a significant benefit from adding adjuvant chemotherapy."

The groundbreaking TAILORx results, presented during the Plenary Session at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting and simultaneously published in The New England Journal of Medicine, have elevated the Oncotype DX test to a new standard of care with increasing, and more consistent, use of the test by physicians worldwide for all medically eligible patients. The study is also having an important impact on global reimbursement of the test, most recently in Germany and Italy. Following the German Institute for Quality and Efficiency in Health Care’s (IQWiG’s) positive assessment of the TAILORx results, the German Federal Joint Committee (G-BA) issued an exclusive nationwide reimbursement decision for the Oncotype DX test. In Italy, the Lombardy Regional Authority adopted a resolution to include the test in the Regional Health Service Fees List, thereby making it available as of September 1, 2019, to eligible patients living in the region.

Over the last several months, results of the TAILORx study have also influenced positive treatment guideline updates distinguishing the Oncotype DX Breast Recurrence Score test from prognostic-only tests based on clinical evidence and the critical importance of predicting chemotherapy benefit. The updates include:

The recent update to ASCO (Free ASCO Whitepaper) guidelines, which increased the proportion of women who can be effectively treated without chemotherapy based on the Recurrence Score results, highlighting the importance of testing all medically eligible early-stage breast cancer patients.

The National Comprehensive Cancer Network (NCCN), which updated its guidelines in 2018 to categorize the Breast Recurrence Score test as the only "preferred" test for chemotherapy treatment decision-making for patients with node-negative, early-stage breast cancer. NCCN also classified the Breast Recurrence Score test as the only test that is predictive of chemotherapy benefit.

The new St. Gallen International Breast Cancer Guidelines, which recommend the Oncotype DX test to guide chemotherapy treatment use for patients with hormone-receptor positive, HER-2 negative, early-stage breast cancer with and without lymph node involvement (up to three positive nodes).

The updated ESMO (Free ESMO Whitepaper) guidelines for early-stage breast cancer, which elevated the Oncotype DX test to highest 1A level of evidence and refer to TAILORx and PlanB results, which identify groups of patients – both in the node-negative and node-positive setting – for whom chemotherapy can be safely spared.

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. The company’s flagship product, the Oncotype DX Breast Recurrence Score test, is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. In prostate cancer, the Oncotype DX Genomic Prostate Score test predicts disease aggressiveness and further clarifies the current and future risk of the cancer prior to treatment intervention, and the Oncotype DX AR-V7 Nucleus Detect test helps determine which patients with metastatic castration-resistant prostate cancer (mCRPC) are resistant to androgen receptor (AR)-targeted therapies. The Oncotype DX AR-V7 Nucleus Detect test is performed by Epic Sciences at its centralized, CLIA-certified laboratory in San Diego and offered exclusively by Genomic Health. With more than 1 million patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeIQ.com, www.MyBreastCancerTreatment.org or www.MyProstateCancerTreatment.org.

On September 30, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis), for the treatment of various cancers including leukemia, prostate and colorectal, reported that results from the Company’s Phase 1b/2 study of onvansertib in patients with relapsed/refractory acute myeloid leukemia (AML) were presented in an oral plenary session at the 2019 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Conference in Barcelona, Spain, on Saturday, September 28th (Press release, Trovagene, SEP 30, 2019, View Source [SID1234539941]). The presentation highlighted the favorable safety profile and clinical efficacy of onvansertib, as well as correlative biomarker data from the recently completed Phase 1b trial.

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The oral presentation at ESMO (Free ESMO Whitepaper) is available for download from the Scientific Presentations page on the Trovagene website at View Source

"These data from this ongoing clinical trial in patients with relapsed/refractory AML support that the combination of onvansertib with either low dose cytarabine or decitabine appear to be feasible, safe and well tolerated up through the 60mg/m2 dose of onvansertib," said Dr. Amer Zeidan, lead investigator and assistant professor of Medicine at the Yale School of Medicine, and Hematology expert at Yale Cancer Center. "While the recently completed dose escalation part of the study focused on evaluating the safety of the combinations, we see evidence of clinical activity, particularly with onvansertib in combination with decitabine. We hope to better understand the efficacy profile of this combination as we go into the Phase 2 expansion part of the trial."

"We continue to be encouraged by our biomarker data which indicates a correlation between biomarker positive patients and their response to treatment with onvansertib," said Dr. Mark Erlander, Chief Scientific Officer of Trovagene. "As we move forward, we plan to further develop the biomarker assay to enable us to proactively identify patients who are most likely to respond to treatment."

Oral Presentation Highlights

Background:

Onvansertib is an oral, highly-selective Polo-like Kinase 1 (PLK1) inhibitor with a half-life of ~24 hours
PLK1 inhibition by onvansertib, assessed via a simple blood test and shown as changes in the phosphorylation of its direct substrate, the translational controlled tumor protein, TCTP, is a biomarker for identifying patients most likely to respond to treatment
Patients eligible for enrollment in the Phase 1b/2 trial are treatment naïve and not candidates for induction therapy or have relapsed/refractory disease to up to 3 prior regimens (Phase 1b) and 1 prior regimen (Phase 2), including those resistant to treatment with venetoclax
Treatment Summary as of June 1, 2019

Safety and Tolerability:

Treatment was well tolerated with no unexpected toxicities reported
No dose limiting serious adverse events or trial related deaths were attributed to onvansertib (Grade 3 or 4 adverse events possible related to onvansertib included 10 (30%) hematologic and 1 (3%) non-hematologic)
The maximum tolerated dose (MTD) was not reached through onvansertib dose level of 60mg/m2, but was subsequently achieved at the 90mg/m2 dose level
Preliminary Efficacy:

In the onvansertib plus decitabine arm, of the 12 patients evaluable for efficacy at onvansertib doses ranging from 12mg/m2 to 40mg/m2, 3 patients achieved the primary efficacy endpoint of objective response (2 CRs – 1 at onvansertib 27mg/m2, 1 at onvansertib 40mg/m2 and 1 CRi at onvansertib 27mg/m2)
In the onvansertib plus low-dose cytarabine arm, of the 12 patients evaluable for efficacy at onvansertib doses ranging from 12mg/m2 to 40mg/m2, 1 patient achieved the primary efficacy endpoint of objective response (CRi at onvansertib 40mg/m2); LDAC arm was discontinued following completion of onvansertib 60mg/m2 cohort
Phase 1b has been successfully completed and the Phase 2 open-label, single-arm trial is enrolling patients for treatment with the recommended Phase 2 dose (RP2D) of onvansertib at 60mg/m2 in combination with decitabine to continue assessing safety and efficacy
Biomarker Analysis:

Of the 24 evaluable patients, 9 (38%) were biomarker positive across both arms
There is a strong correlation between biomarker positive patients and response to treatment with onvansertib; 6 of 9 biomarker positive patients had a decrease in bone marrow blasts of ≥ 50%, versus 1 of 11 in the biomarker negative patients
Among the 4 patients with CR (CR + CRi) 3 were biomarker positive and 1 was borderline biomarker positive
Further biomarker validation is continuing including development of a second-generation assay that is more sensitive and quantitative
About the Phase 2 Clinical Trial of Onvansertib in AML

The Phase 2 AML trial (NCT03303339) of onvansertib in combination with decitabine will enroll 32 patients who are either treatment naïve and not candidates for induction therapy or who have relapsed disease after treatment with one prior regimen. Patients will receive onvansertib, administered orally, on days 1 through 5 of each 21-28-day cycle in combination with decitabine. The primary efficacy endpoint of objective response (CR + CRi) will be assessed in patients who complete at least 1 cycle of treatment.

About Onvansertib

Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.

Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410); and a Phase 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML (NCT03303339). Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.

Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.