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Clinical Response and Translational Data from DeCidE1, a Phase 2 Study of DPX-Survivac Immunotherapy in Patients with Advanced Recurrent Ovarian Cancer

On May 29, 2020 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical-stage biopharmaceutical company pioneering a novel class of targeted cancer immunotherapies and vaccines against infectious diseases, reported updated clinical response and translational data from DeCidE1, its Phase 2 study evaluating the safety and efficacy of DPX-Survivac with intermittent low-dose cyclophosphamide (CPA) in patients with recurrent, advanced platinum-sensitive and -resistant ovarian cancer (Press release, IMV, MAY 29, 2020, View Source [SID1234558686]).

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Results from the ongoing study showed prolonged durable clinical responses, alongside favorable tolerability, and strong translational data linking the observed clinical benefit with DPX-Survivac’ mechanism of action. Oliver Dorigo, M.D., Ph.D., Principal Investigator of the DeCidE1 study, is presenting these results in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 (ASCO20) Virtual Scientific Program.

"IMV’s targeted T-cell therapy continues to elicit a rapid and robust immune response with survivin-specific T cells infiltrating tumors as soon as 56 days post-treatment. These results validate DPX-Survivac’s unique mechanism of action and support the hypothesis that survivin-specific T cells can translate into clinical benefits when sustained over an extended period of time," said Dr. Dorigo associate professor and director of gynecologic oncology at Stanford University. "These results support DPX-Survivac as a new and much-needed treatment option, with potential to improve the quality of life in women with recurrent late-stage ovarian cancer, a hard-to-treat indication where other immunotherapies have so far had limited success."

"With these results, DPX-Survivac continues to exhibit significant and durable anti-tumor activity, paving the way for targeted T cell therapies in advanced recurrent ovarian cancer and other solid tumors. In particular, we are quite pleased to observe an additional patient with stable disease (SD) convert to partial response (PR), implying the potential for responses to deepen over time

with ongoing therapy. Additionally, DPX-Survivac continues to be well tolerated, which is especially meaningful compared to single-agent chemotherapy and other approaches in development," said Joanne Schindler, M.D., D.V.M., Chief Medical Officer at IMV. "We believe these results highlight DPX-Survivac’s potential to alter the treatment landscape in advanced ovarian cancer and support its continued development. We look forward to providing updates from other studies evaluating DPX-Survivac, in multiple solid tumors and r/r DLBCL, later this year."

Updated Results from DeCidE1

As of data cut-off date, May 2, 2020, 19 patients were evaluable for efficacy with four patients (21%) still receiving treatment. Notably, 18/19 evaluable patients had stage 3 or 4 disease at time of diagnosis, the majority of whom had received >3 lines of prior therapy and were platinum resistant. Key findings on the safety and efficacy of DPX-Survivac/CPA are outlined below:

5/19 patients (26%) achieved a PR with tumor regression >30% on target lesions

15/19 patients (79%) achieved disease control, defined as Stable Disease (SD) or Partial Response (PR) on target lesions

Tumor shrinkage of target lesions was observed in 10 patients (53%)

Overall, treatment was well-tolerated. The majority of treatment-related adverse events reported were Grade 1 events and related to reactions at the injection site.

Durable clinical benefits lasting ≥ 6 months were observed in seven patients (37%)

5/7 patients (71%) have now reached duration of clinical benefit > 10 months including three patients with PR and two patients with SD

The two patients with SD are about to reach the 1-year mark

Translational analyses on longitudinally collected peripheral blood mononuclear cell (PBMC) and tumor tissue samples link observed clinical benefit and survivin-specific T cells, supporting DPX-Survivac’s unique mechanism of action. Key translational findings are outlined below:

Treatment generated a survivin-specific CD8+ T cell response in PBMC samples of 14/16 (87%) evaluable patients.

Treatment induced infiltration of survivin-specific T cell clones into the tumors as early as day 56 following treatment, which was shown in an analysis of the TCR² repertoires in five subjects who achieved stable disease.

These data are presented in a poster session (Abstract Number: 6075) at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program, available on-demand to ASCO (Free ASCO Whitepaper)20 participants beginning at 8:00 am ET on Friday, May 29, 2020. A copy of the poster is available under "Scientific Posters" in the "Events, Webcasts & Presentations" section of IMV’s website.

About the DeCidE1 Study

"DeCidE1" is a Phase 2 multicenter, open-label study evaluating the safety and effectiveness of DPX-Survivac, with intermittent low-dose cyclophosphamide (CPA) used as an immunomodulator to increase the level of survivin-specific T cells. This Phase 2 arm enrolled 19 evaluable patients with recurrent, advanced platinum-sensitive and –resistant ovarian cancer. Except for one patient, all patients had stage 3 or 4 disease at time of diagnosis. 12 patients had received 3 or more lines of prior therapy.

Patients received 2 subcutaneous injections of DPX-Survivac three weeks apart and every eight weeks thereafter, and intermittent low dose CPA one week on and one week off for up to 1 year. Paired tumor biopsies were performed prior to treatment and on treatment.

Primary endpoints of this study are overall response rate, disease control rate and safety. Secondary endpoints include cell mediated immunity, immune cell infiltration in paired biopsy samples, duration of response, time to progression, overall survival and biomarker analyses.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of targeted immunotherapies designed to elicit antigen-specific functional, robust and sustained de novo T cell response. IMV believes this mechanism of action is key to generating durable solid tumor regressions. DPX-Survivac consists of five unique HLA-restricted survivin peptides formulated in IMV’s proprietary DPX drug delivery platform and known to induce a cytotoxic CD8+ T cell response against survivin expressing cancer cells.

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 chemotherapies. 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.

Ziopharm Oncology Presents Encouraging Clinical Data for Controlled IL-12 for the Treatment of Recurrent Glioblastoma at the 2020 American Society of Clinical Oncology

On May 29, 2020 Ziopharm Oncology, Inc. (Nasdaq: ZIOP), reported the presentation of final clinical data from its phase 1 monotherapy ("Main") study of Controlled IL-12, Ad-RTS-hIL-12 plus veledimex (Ad+V), as well as updated clinical data from two phase 1 substudies of Ad+V, a monotherapy expansion study ("Expansion") and a combination study with a PD-1 inhibitor, for the treatment of adult recurrent or progressive glioblastoma multiforme (rGBM) at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual (Virtual) Meeting (Press release, Ziopharm, MAY 29, 2020, View Source [SID1234558685]).

"The results we have seen from the two Controlled IL-12 monotherapy studies are particularly promising, with median overall survival in unifocal patients after monotherapy Ad+V treatment remaining at 16.2 months after longer term follow-up, as well as encouraging preliminary data from the PD-1 combination study where median overall survival has not yet been reached," said Dr. Antonio Chiocca, M.D., Ph.D., Trial Investigator and Professor of Neurosurgery at Harvard Medical School, Surgical Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute, and Chairman of Neurosurgery and Co-Director of the Institute for the Neurosciences at Brigham and Women’s Hospital. "We also reported three additional partial responses, one in the monotherapy Main study, one in the Expansion study and one in the combination study, bringing the total number of partial responses (PRs) to five. Observing responses in brain tumors in the setting of recurrence is unusual and highly encouraging, and, along with the survival data, highlight the potential of Ad+V for the treatment of rGBM."

Laurence Cooper, M.D., Ph.D., Chief Executive Officer of Ziopharm, added, "According to most recent data, even with the best available therapies, median overall survival for unifocal rGBM patients appears to be 6-12 months. We are therefore heartened by the collection of data presented at ASCO (Free ASCO Whitepaper) across our three studies, which demonstrate survival benefits beyond a year supported by imaging studies showing tumor regression and biopsies revealing that Ad+V administration turns ‘cold’ tumors ‘hot’ by recruiting T cells into the tumor. We look forward to continuing to report follow-up monotherapy and combination phase 1 data, as well as initial data from the ongoing phase 2 study of Ad+V in combination with Libtayo, which is nearing completion of enrollment."

Ad-RTS-hIL-12 plus 20 mg/day veledimex is currently being examined in a phase 1 monotherapy "Expansion" substudy for the treatment of rGBM (NCT03679754) that enlarged the phase 1 "Main" veledimex dose escalation trial (NCT02026271) by an additional 36 patients. New clinical results in monotherapy were shared in poster presentations.

Final data highlights from the "Main" dose escalation monotherapy study, titled "Final results of Controlled IL-12 Monotherapy in Adults with Grade III or IV Gliomas," (Abstract #3040) include:

Subjects (n=6, unifocal, craniotomy) who received low-dose (≤ 20 mg cumulative) corticosteroids during veledimex dosing (Days 0 to 14, coinciding with administration of veledimex) had a median overall survival (mOS) of 17.8 months (mean follow-up of 18.4 months)
15 subjects (n=14, unifocal, craniotomy) treated with Ad (Day 0) and 20 mg veledimex with any dosing of corticosteroids had a mOS of 12.7 months (mean follow-up of 13.1 months)
Serial MRIs show patient with confirmed PR at 72 weeks, with durability at 96 weeks and monitoring ongoing
Veledimex-dependent and proportional increases in IL-12 and IFN-γ, resulting in immune activation
Favorable safety profile:
Ad+V was safely administered and tolerable in both craniotomy (Group 1, n=31) and stereotactic subjects (Group 2, n=7)
52 serious adverse event (SAEs) were reported in 21 subjects (55%) and 14 related SAEs were reported in 12 subjects (32%). There have been no study treatment related deaths
The 20 mg veledimex dose is the recommended phase 2 dose as confirmed in the "Expansion" substudy focusing on veledimex 20 mg (n=36; ASCO (Free ASCO Whitepaper) 2020 #2564)
The 10 mg veledimex dose level was studied to move forward as the starting dose in the monotherapy study for pediatric subjects (NCT03330197) and in combination therapy with PD-1 inhibitor in adults with rGBM (ASCO 2020 #2510)
Data highlights from the "Expansion" study, titled "Survival of Subjects with Recurrent Glioblastoma Receiving Intratumoral Administration of Controlled IL-12 with Limited Exposure to Dexamethasone," (Abstract #2564) include:

Subjects receiving Ad (Day 0, craniotomy) and 20 mg (Days 0 to 14) veledimex with unifocal disease ("Main" and "Expansion" n=20) administered low-dose corticosteroids showed mOS of 16.2 months (mean follow-up of 14.1 months)
Serial MRIs show patient with previously reported pseudoprogression now has confirmed PR at 30 weeks and response durability out to 48 weeks (follow-up ongoing), in addition to the PR previously reported 1
Adverse reactions remained consistent with previously reported results, being predictable and promptly reversible upon discontinuation of veledimex, and there were no drug-related deaths
Veledimex dosing compliance was comparable to and slightly higher than the "Main" study
Combination of Ad+V with the PD-1 inhibitor nivolumab (nivo) is being examined in a phase 1 substudy for the treatment of rGBM (NCT03636477). Data highlights shared in a poster discussion titled "Controlled IL-12 in Combination with a PD-1 Inhibitor: Subjects with Recurrent Glioblastoma" (Abstract #2510) include:

mOS has not been reached, with mean follow-up at 8.3 months
Drug-related toxicities were comparable to monotherapy, being predictable, dose-related, and promptly reversible upon discontinuation of veledimex
As previously reported from Ad+V monotherapy, plasma pharmacokinetics (PK) demonstrates an exposure-response relationship for veledimex
Serum IL-12 was detected in all subjects following initiation of Ad+V, typically followed by a transient increase in downstream serum IFN-γ, which is consistent with previously reported data of Ad+V monotherapy
There is evidence of immune-mediated anti-tumor effects, with serial MRIs showing pseudoprogression and one new PR, in addition to the PR previously reported2
To further investigate Ad+V in combination with an immune checkpoint inhibitor in rGBM subjects, a phase 2 trial of Ad+V in combination with cemiplimab-rwlc (Libtayo) is currently ongoing (NCT04006119).

More information about Controlled IL-12 is available on the Company’s website at View Source Additionally, the posters presented at the ASCO (Free ASCO Whitepaper) 2020 Virtual Meeting will be available on the Company’s website in the "Scientific and Medical Publications" section.

Quest Diagnostics to Speak at the Jefferies Virtual Healthcare Conference

On May 29, 2020 Quest Diagnostics Incorporated (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that it is scheduled to speak at the Jefferies Virtual Healthcare Conference (Press release, Quest Diagnostics, MAY 29, 2020, View Source [SID1234558684]). Mark Guinan, Executive Vice President and CFO and Jim Davis, Executive Vice President, General Diagnostics, will discuss the company’s vision, goals and two-point strategy to accelerate growth and drive operational excellence, and the company’s current perspective on the impact of the COVID-19 pandemic. The presentation is scheduled for Wednesday, June 3, 2020 at 1:30 p.m. Eastern Time.

The presentation will be webcast live during the conference and will be available on the company’s investor relations page which can be accessed at ir.QuestDiagnostics.com. In addition, the archived webcast will be available within 24 hours after the conclusion of the live event and will remain available until July 3, 2020.

GlycoMimetics to Present at Upcoming Jefferies Virtual Healthcare Conference

On May 29, 2020 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that Chief Executive Officer Rachel King will provide a company overview at the upcoming Jefferies Virtual Healthcare Conference (Press release, GlycoMimetics, MAY 29, 2020, View Source [SID1234558683]). The presentation will be available on the company’s website at the "Investors" tab for 30 days, beginning Thursday, June 4 from 1:00 – 1:25 p.m. EDT.

To access the live webcast and subsequent archived recordings for the presentation, please visit the GlycoMimetics website at View Source

Dana-Farber researchers present key studies at ASCO annual meeting

On May 29, 2020 Dana-Farber Cancer Institute reported are presenting dozens of research studies at the 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Dana-Farber Cancer Institute, MAY 29, 2020, View Source [SID1234558682]). The studies will be presented online during the virtual scientific program taking place May 29-May 31. ASCO (Free ASCO Whitepaper) is the world’s largest clinical cancer research meeting, attracting more than 30,000 oncology professionals from around the world.

The findings show new treatments and diagnostic advances in breast and lung cancers, lymphoma, kidney, and many others, as well as looking at using video education to guide care, and racial and ethnic disparities in cancer care. Some of the research highlights include:

Interim analysis of ZUMA-5: A phase 2 study of axicabtagene ciloleucel in patients with relapsed/refractory indolent non-hodgkin lymphoma

Author: Caron Jacobson, MD

Abstract: 8008

The vast majority of patients with follicular lymphoma or marginal zone lymphoma – two slow-growing forms of non-Hodgkin leukemia – responded to and benefited from a novel CAR T-cell therapy in a recent clinical trial, Dana-Farber Cancer Institute investigators report. The 140 participants (124 with follicular lymphoma, 16 with marginal zone lymphoma) in the ZUMA-5 trial had received a median of three treatments for their disease prior to treatment with axicabtagene ciloleucel, a CAR T-cell therapy that targets CD19 receptors on cancerous cells. Ninety-three percent of the patients showed a response to the therapy, including 80% who had a complete response – an absence of detectable cancer following treatment. In patients with an initial complete response, 80% maintained that response after a median follow-up of 15.3 months. The most common adverse effects of the therapy were neutropenia, anemia, and decreased neutrophil count, which generally were manageable. The rate of high-grade neurotoxicity was 15%. Among patients with follicular lymphoma, 23% had no cytokine release syndrome, and the median time to onset was four days, which may allow for outpatient dosing in the future.

Tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB)

Author: Nancy Lin, MD

Abstract: 1005

In patients with HER2+ metastatic breast cancer that has spread to the brain, combining the HER2-inhibiting agent tucatinib with trastuzumab and capecitabine can significantly delay the advance of the disease in the brain and extend patients’ lives, a clinical trial led by Dana-Farber Cancer Institute investigators has demonstrated. The HER2CLIMB study compared the three-drug regimen to trastuzumab and capecitabine alone in 291 patients whose breast cancer had metastasized to the brain. Participants in the tucatinib group experienced a median of nine months before the brain metastases grew worse, compared to 4.2 months for the non-tucatinib group, and survived a median of 18.1 months compared to 12 months for the non-tucatinib group. Based on results of HER2CLIMB, the FDA granted approval of the three-drug regimen on April 17, 2020, for the treatment of adult patients with advanced inoperable or metastatic HER2+ breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

A multicenter phase 2 study of venetoclax plus dose-adjusted R-EPOCH (VR-EPOCH) for Richter’s syndrome

Author: Matthew S. Davids, MD, MMSc

Abstract: 8004

Adding a relatively new targeted drug, venetoclax, to a standard chemoimmunotherapy regimen has shown promising activity in Richter’s syndrome, a transformation of a more indolent disease, chronic lymphocytic leukemia, into an aggressive form of non-Hodgkin lymphoma (NHL) with a particularly poor prognosis, say researchers from Dana-Farber. There is no standard of care for treatment, but a commonly used regimen is R-EPOCH, a combination of four chemotherapeutic agents plus rituximab, a monoclonal antibody immunotherapy drug. Although R-EPOCH is highly effective for some forms of NHL, in Richter’s syndrome the rate of complete response is only about 20%, and the average survival is only three to six months.

Venetoclax, the first of a class of drugs known as BCL2 inhibitors, had a 43% overall response rate as a single agent in small cohort of patients with Richter’s syndrome in a phase 1 study. In the current study, venetoclax was combined with R-EPOCH (VR-EPOCH) with the rationale that the venetoclax may work as a "chemosensitizing" agent to help the chemotherapy be more effective. This single-arm, phase 2 investigator-initiated multicenter study enrolled 26 patients at Dana-Farber, MD Anderson, and Ohio State. In the 20 patients who began combination therapy, 16 (80%) responded, including 13 (65%) who had complete response as best response. Eight patients had allogeneic stem cell transplants, with the first such patient now still in complete remission over two and half years after completing transplant. Patients who were not transplant candidates could continue on venetoclax maintenance, and the longest such patient has now been in complete remission for over two years after completing the chemotherapy portion of the study. The side effects were typical of those seen with R-EPOCH alone, including infections and low blood counts.

Matthew S. Davids, MD, MMSc, is the principal investigator and first author of the study and said about two-thirds of the patients who started the VR-EPOCH combination achieved complete remission, far higher than the 20% achieved historically with R-EPOCH alone and this chemosensitization strategy will be further explored in additional studies in this patient population.

Idecabtagene vicleucel, a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma; initial KarMMa results

Author:Nikhil Munshi, MD

Abstract: 8503

A potential CAR T-cell therapy that targets a key plasma cell antigen on cancer cells produced deep and lasting responses in patients with relapsed and treatment-resistant multiple myeloma who had undergone several previous treatments, according to preliminary data from an international clinical trial led by Dana-Farber Cancer Institute researchers. The 128 patients in the KarMMa study were treated with idecabtagene vicleucel, a genetically engineered CAR T-cell therapy made from patients’ own T cells that targets the B-cell maturation antigen (BCMA) on myeloma cells. After a median follow-up of 13.3 months, 73.3% of participants had a partial or complete response to the therapy, and the median interval before the disease worsened was 8.6 months, both of which were higher at increased doses. The most common adverse effects were cytopenia (a low red blood cell count) and cytokine release syndrome, a common side effect of CAR T-cell therapies.

A randomized controlled trial of video education or in-person genetic counseling for men with prostate cancer

Author:Huma Q. Rana, MD

Abstract: 1507

This study compared a novel video education method with in-person genetic counseling in advance of genetic testing for men with potentially lethal prostate cancer and found no significant differences in acceptability of genetic testing. Although the study has not been completed, this randomized trial suggests that video education can be used to improve access to cancer genetics education and testing to patients who, for various reasons including the coronavirus pandemic, lack access to in-person genetic counseling.

Led by Huma Q. Rana, MD, and Mary-Ellen Taplin, MD, the trial, called ProGen, recruited men with potentially lethal prostate cancer. This includes metastatic disease, a high Gleason score, rising PSA (prostate specific antigen) after local therapy, diagnosis at age 55 or younger, and other factors. Rana found 13% of subjects had pathogenic or likely pathogenic variants in cancer susceptibility genes; 32% of subjects with a positive result had pathogenic variants were in BRCA1 and BRCA2. Identifying those variants through genetic testing may lead to targeted therapy and can guide cancer surveillance. Genetic testing is recommended to these patients, but access to genetic counseling and testing is limited by strained resources. The ProGen study examined a novel video pretest model aimed at providing access to genetic testing for men who have been traditionally underserved/unrepresented in cancer genetics clinics.

Over a two-year period, 662 men were randomized 3:1 to video education or genetic counseling in person. At the time of the intervention, most men agreed or strongly agreed that their assigned arm – video or in-person – was useful. The researchers concluded that both the novel video education modality and traditional genetic counseling "yielded high genetic testing uptake without significant differences in outcome measures of acceptability and satisfaction."

US trends and racial/ethnic disparities in opioid access among patients with poor prognosis cancer near end of life

Author:Andrea Enzinger, MD

Abstract: 7005

Efforts to mitigate the opioid addiction crisis may have unintended consequences for cancer patients near the end of life, particularly for black patients and other racial/ethnic minorities. According to a recent Dana-Farber study, cancer patients’ access to opioids at the end-of-life has decreased substantially since 2007, with even greater declines among African Americans.

Andrea Enzinger, MD, is first author of this study which included 243,124 Medicare patients with poor prognosis cancers who died between 2007 and 2016. The analysis revealed that the proportion of cancer patients filling an opioid prescription in the 30 days before death or hospice enrollment fell from 41.7% to 35.7% over the study period, with greater decreases among black patients (39.3% to 29.8%) than white patients (42.2% to 36.5%). Use of long-acting opioids, which are important for managing severe cancer pain, also fell from 17% in 2007 to 12% in 2016. Blacks patients were also significantly less likely than white patients to be prescribed long-acting opioids and were prescribed significantly lower doses of opioids. Rates of emergency department visits for pain near the end of life increased from 13.2% to 18.8% over the study period. Again, black patients were significantly more likely than whites to receive care for their pain in an emergency department.

The researchers concluded that cancer patients’ access to opioids near the end-of-life decreased substantially from 2007 to 2016, while pain-related visits to emergency departments increased. Along with this trend, the scientists report that there are significant racial and ethnic disparities in opioid access, with black patients receiving fewer opioids at lower doses, and having more emergency-department-based care for pain near the end of life.