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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.

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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.

CytomX Therapeutics Clinical Programs Highlighted at American Society of Clinical Oncology ASCO20 Virtual Scientific Program

On May 29, 2020 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, reported the availability of oral and poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program taking place from May 29 – May 31, 2020 (Press release, CytomX Therapeutics, MAY 29, 2020, View Source [SID1234558680]).

"A comprehensive body of evidence was presented today at ASCO (Free ASCO Whitepaper) 2020 that continues to validate our approach to conditional antibody activation and therapeutic target engagement with the Probody platform," said Amy Peterson, M.D., chief development officer of CytomX Therapeutics. "The seven presentations collectively highlight the potential of the Probody platform to enable successful engagement of previously undruggable targets, like CD71 and CD166, and create next generation immune-checkpoint inhibitors such as the anti-PD-L1 Probody therapeutic, CX-072, and BMS-986249, a Probody version of ipilimumab. The findings underpin the advancement of all four drug candidates into Phase 2 and our commitment to bringing meaningful advances to patients living with cancer."

CX-2029: Validating CD71 As A First-in-Class Oncology Target

In the oral abstract 3502, Dr. Melissa Johnson of the Sarah Cannon Research Institute at Tennessee Oncology, presented preliminary clinical data from the first-in-human, dose-escalation, monotherapy Phase 1 study of CX-2029, a Probody drug conjugate (PDC) targeting CD71 (transferrin receptor). CX-2029 is conjugated to the cytotoxic payload MMAE and is being developed by CytomX in partnership with AbbVie. As of an April 20, 2020 data cutoff, 45 patients with advanced solid tumors were enrolled into 8 escalating dose cohorts between 0.1 mg/kg – 5 mg/kg CX-2029 administered intravenously every three weeks.

Evidence of target lesion reduction was seen, principally in patients with tumors of squamous histology. (Figure 1)
° 3 confirmed partial responses were observed in 17 response-evaluable patients treated at doses ≥2 mg/kg of CX-2029, 2 in patients with squamous non-small cell lung cancer (SqNSCLC) and 1 in a patient with head and neck squamous cell cancer (HNSCC).
° 2 of the partial responses (both at the 3 mg/kg dose) were confirmed after the April 20th cutoff date.
CX-2029 Waterfall Plot (Doses 2–5 mg/kg)

CX-2029 Waterfall Plot (Doses 2–5 mg/kg)
Figure 1 is available at View Source

Safety Profile Supports Recommended Phase 2 Dose of 3 mg/kg, Every Three Weeks

CX-2029 was generally well tolerated at doses up to 3 mg/kg.
At doses of 0.25 – 5 mg/kg, CX-2029 circulated predominantly as the intact species (>90%).
The most common treatment related adverse events (TRAE) were infusion related reactions, anemia, and neutropenia/leukopenia.
° Infusion related reactions were mostly Grade 1/2, occurred at the first dose, were not dose dependent and resolved upon initiation of supportive care.
° Hematologic TRAEs Grade ≥ 3 were dose dependent.
• Anemia and neutropenia are commonly observed with the MMAE payload.
• Anemia was managed with transfusions and supportive care.
No CX-2029 treatment related deaths were reported and late onset Grade 3/4 TRAEs were predominately anemia and neutropenia.
The etiology of anemia is under investigation and is likely multifactorial, including MMAE-related and CD71 expression on red blood cell precursors.
CytomX is preparing to advance the dose of 3 mg/kg of CX-2029 administered every 3 weeks into 4 dose-expansion cohorts: HNSCC, SqNSCLC, esophageal carcinoma and diffuse large B cell lymphoma.
"Targeting CD71 with this novel approach has the potential to address areas of unmet medical need in difficult to treat tumor types, improving patient benefit," said Melissa L. Johnson, M.D., CX-2029 principal study investigator and associate director of lung cancer research at Sarah Cannon Research Institute at Tennessee Oncology. "This first-in-human data of CX-2029 establishes the transferrin receptor as a high potential anticancer target addressable with CytomX’s Probody technology."

CX-2009: Encouraging Clinical Activity Supports Advancement in HER2 Negative Breast Cancer

In Poster 18, Dr. Valentina Boni of START Madrid-CIOCC, presented updated data on CX-2009, a PDC targeting CD166 and conjugated to the cytotoxic payload DM4. As of an April 20, 2020 data cutoff, 96 patients were enrolled into the dose escalation Phase 1 study and received CX-2009 at escalating doses of 0.25 – 10 mg/kg every 3 weeks (86 patients) or 4 – 6 mg/kg every 2 weeks (10 patients).

Durable Clinical Activity Observed in HER2 Negative (HER2-) Breast Cancer

Evidence of target lesion reduction was observed at doses or dose equivalents of ≥4 mg/kg every 3 weeks across 68 evaluable patients including those with HER2- breast cancer, ovarian cancer, NSCLC and HNSCC.
° HER2- breast cancer patients were heavily pretreated with a median of 7 prior lines of therapy.
26 patients with HER2– breast cancer who received ≥4 mg/kg of CX-2009 were response-evaluable:
° 2 confirmed partial responses were observed, both in patients with hormone receptor positive (HR+) breast cancer.
° 3 unconfirmed responses were observed in patients with triple negative breast cancer (TNBC).
° Clinical benefit rates of 39% and 35% were observed at 16 and 24 weeks (CBR16 and CBR24, respectively).
• All 4 TNBC patients who achieved CBR16 also achieved CBR24.
CX-2009 Waterfall Plot and Spider Plot: HER2- Breast Cancer (≥4 mg/kg Every 3 Weeks)

CX-2009 Waterfall Plot and Spider Plot
Figure 2 is available at View Source

Safety Profile Supports Recommended Phase 2 Dose of 7mg/kg, Every 3 Weeks

CX-2009 was generally well tolerated at doses up to 7 mg/kg administered every three weeks.
No dose limiting toxicities (DLTs) were reported at doses up to 7 mg/kg.
DM4-related toxicities, including ocular, neuropathic, and hepatic were higher in frequency at dose equivalents greater than 7 mg/kg dosed at every three weeks compared to 7 mg/kg or lower.
° Occurrence and severity of ocular adverse events were dose dependent: One Grade 3+ event was observed in a patient treated at 5 mg/kg, none at 7 mg/kg.
° 20% of patients dosed at ≥8 mg/kg experienced Grade 3+ ocular adverse events.
Preliminary pharmacokinetic (PK) data showed that CX-2009 circulates predominantly intact at all doses and PK is not strongly influenced by target-mediated drug disposition or anti-drug antibodies (ADAs). (Poster 329)
In December 2019, CytomX announced the initiation of a Phase 2 expansion study of CX-2009 monotherapy at 7 mg/kg administered every three weeks in up to 40 patients with hormone receptor (ER, PR) positive, HER2 negative breast cancer. In March 2020, CytomX announced the decision to temporarily pause new patient enrollment and new site activation in this study due to the impact of the COVID-19 pandemic. CytomX continues to closely monitor emerging Health Authority guidance and IRB/Ethics Committee recommendations and intends to resume the CX-2009 clinical program as soon as practicable.

"Patients with advanced breast cancer continue to need treatment options, this is especially true for patients with hormone receptor positive and HER2 negative breast cancer that is refractory to hormonal based therapies," said Alison L. Hannah, M.D., chief medical officer of CytomX Therapeutics. "We believe that targeting CD166, previously considered undruggable as an oncology target, using our Probody drug conjugate platform, may provide a unique treatment opportunity for this patient population. The data in patients with triple negative breast cancer are equally interesting and support the advancement of CX-2009 monotherapy into Phase 2 where we will also evaluate CX-2009 in combination with CX-072, our Probody therapeutic directed against PD-L1."

CX-072: Anti-PD-L1 Probody Checkpoint Inhibitor

In the oral presentation of Abstract 3005 by Dr. Fiona Thistlethwaite of The Christie NHS Foundation Trust at the University of Manchester, updated data were presented from the Phase 1/2 trial of PROCLAIM-CX-072 monotherapy and CX-072 in combination with ipilimumab with a focus on patients who received long-term treatment, defined as ≥ 6 months of treatment. The CX-072 10 mg/kg monotherapy expansion arm enrolled 114 patients in seven tumor types.

As of an April 20, 2020 data cutoff, CX-072 monotherapy continued to demonstrate durable anti-tumor activity in patients with IO sensitive tumors such as TNBC, anal squamous cell carcinoma (aSCC), cutaneous squamous cell carcinoma (cSCC) and tumors with high mutational burden (hTMB).
As of the same data cutoff, CX-072 in combination with ipilimumab had been administered to 27 patients with advanced solid tumors. Durable anti-cancer activity was observed including one complete response in a patient with aSCC who remains on study more than two years after first dose.
Of the 141 patients across the monotherapy and combination arms: 34 patients received long term treatment in the monotherapy arm (median 11.3 months), and 6 patients received long term treatment in the combination arm (median 21.3 months).
Grade 3/4 TRAEs were 10% and 5.9% for who received monotherapy < 6 months and ≥ 6 months, respectively, and 33% in each group in the combination arm.
Long term patients experienced fewer irAEs and had no grade 3+ irAEs suggesting that tolerability early on can impact duration of treatment.
Preliminary clinical PK data (Poster 332) and translational analyses of pre- and on-treatment biopsies (Poster 172) were supportive of the Probody mechanism of action.
CX-072 Monotherapy Waterfall Plots and Spider Plots (10 mg/kg)

CX-072
Figure 3 is available at View Source

Continued Dr. Hannah "Our ASCO (Free ASCO Whitepaper)20 clinical, translational, and pharmacokinetic presentations on CX-072 reinforce previously presented data and show clear evidence of anti-cancer activity and favorable tolerability for this unique checkpoint inhibitor. These integrated data support a differentiated profile for CX-072 that we believe can be of potential utility as a unique combination partner for other anti-cancer agents, including CX-2009."

BMS-986249: Anti-CTLA-4 Probody Demonstrates Encouraging Safety Profile in Phase 1 Trial

Bristol Myers Squibb presented dose escalation data from their Phase 1/2 trial of BMS-986249, a Probody version of the anti-CTLA-4 antibody ipilimumab in Abstract 3508. This trial assessed the safety, pharmacokinetics and pharmacodynamics of escalating doses of BMS-986249 as monotherapy or in combination with the anti PD-1 antibody nivolumab in patients with advanced cancers. The doses of BMS-986249 ranged from 240 mg to 2400 mg (approximately 3 – 30 mg/kg). BMS-986249 was generally well tolerated as monotherapy and in combination with nivolumab. Bristol Myers Squibb has initiated a randomized clinical trial to explore various doses of BMS-986249 in combination with nivolumab in patients with advanced melanoma.

ASCO20 Virtual Scientific Program – Posters and Presentations

Copies of the ASCO (Free ASCO Whitepaper)20 presentations and posters are available under the Scientific Publications section of the CytomX website at www.CytomX.com.

Conference Call and Webcast

CytomX senior management will host a conference call and live webcast with slides today, Friday, May 29, 2020, from 5:00 p.m. – 6:00 p.m. ET/ 2:00 p.m. – 3:00 p.m. PT to discuss these presentations. This event can be accessed in three ways:

From the CytomX website: View Source Please access the website 15 minutes prior to the start of the call to download and install any necessary audio software.

By telephone: Participants can access the call by dialing 1-877-809-6037 (United States) or 1-615-247-0221 (International) referencing Conference ID 4267278.

By replay: A replay of the webcast will be located under the Investor Relations section of CytomX’s website approximately two hours after the conclusion of the live call and will be available for 30 days following the call.

Constellation Pharmaceuticals to Participate in Investor Conference

On May 29, 2020 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported that the Company will participate in an upcoming virtual investor conference (Press release, Constellation Pharmaceuticals, MAY 29, 2020, View Source [SID1234558679]). Jigar Raythatha, CEO, will present at the Jefferies Virtual Healthcare Conference at 2:30 PM EDT on June 2. A live audio webcast of Mr. Raythatha’s presentation and archives for replay will be available on the Investor Relations section of Constellation’s website at View Source The audio webcast replay will be available for 30 days following the live presentation.