On June 4, 2021 Vincerx Pharma, Inc. (Nasdaq: VINC) a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported the presentation of safety and efficacy data from the Phase 1 study of VIP152, the Company’s PTEFb/CDK9 inhibitor, in patients with double-hit lymphoma at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held virtually from June 4-8, 2021 (Press release, Vincerx Pharma, JUN 4, 2021, View Source [SID1234583562]).

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"The data generated in double-hit lymphoma are compelling, providing early evidence that on-target activity of VIP152 has the potential to provide durable responses in patients who have no standard of care therapy and poor prognoses," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx. "The achievement of durable metabolic complete responses with once weekly monotherapy lasting beyond two and three years is remarkable. These efficacy signals were also obtained with a favorable safety profile, with no patients stopping treatment due to adverse events, and the patients with metabolic complete responses stopping treatment only due to the COVID-19 pandemic. Our Phase 1 results, which also include durable disease control in solid tumors, provide a strong foundation of data, which support targeting MYC and MCL1-driven malignancies with our potent and selective PTEFb/CDK9 inhibitor. We look forward to further investigating the potential of VIP152 in challenging patient populations with our ongoing Phase 1b expansion study, which is currently enrolling patients with relapsed/refractory aggressive lymphoma and advanced solid tumors, and our soon to be launched Phase 1b dose-escalation in CLL relapsed/refractory to venetoclax and BTK inhibitors."

Key Presentation Highlights:

Poster presentation, titled, "Safety and efficacy of VIP152, a PTEFb / CDK9 inhibitor, in patients with double-hit lymphoma", include:

CDK9 mediates the transcription of oncogenes such as MYC and MCL-1, which play a critical role in a variety of cancers.
VIP152, a potent and selective inhibitor of CDK9, has completed dose escalation in patients with advanced malignancies (NCT02635672). Significant monotherapy clinical activity was observed with a favorable safety profile:
Seven patients with solid tumors had disease control during the dose escalation portion of the study, including a patient with pancreatic cancer (~14 cycles; dose 30 mg once weekly) and a patient with salivary gland cancer (~24 cycles; dose 22.5 mg once weekly).
One patient with double-hit DLBCL (DHL), who was treated with VIP152 30 mg once weekly, achieved metabolic complete remission. DHL is defined as a dual arrangement or overexpression of the MYC gene and either the B-cell lymphoma 2 (BCL2) or BCL6 genes.
No patients discontinued due to adverse events.
An expansion cohort of 6 additional patients with DHL were dosed with VIP152 30 mg once weekly:
All patients with DHL (median [range] age 70 [58-84] years) had received front-line R-CHOP or R-EPOCH, with two patients having had prior stem cell transplant, and additional therapies include R-DHAP, R-GemOx, R-ICE and durvalumab. Four patients had 2 prior lines of therapy and 3 patients had ≥3 prior lines of therapy. Three patients had been refractory to their last treatment. Six patients had advanced disease (Ann Arbor Stage III or IV) at study entry.
VIP152 had a favorable safety profile, with most common adverse events (AEs) being Grade 1 and Grade 2 severity. Two patients had a serious AE (Grade 3 syncope and Grade 3 tumor pain). No patients withdrew from treatment due to any AEs.
Pharmacodynamic biomarker analysis showed significant reduction, lasting at least 4 hours, of MYC, PCNA and MCL-1 mRNA in all patients.
Anti-tumor activity consisted of 2 metabolic complete responses (CRs) in 7 patients (29%), based on investigator-assessed FDG-PET scans.
Both metabolic CRs were durable, with patients remaining on treatment for 3.7 and 2.3 years until study withdrawal due to the COVID pandemic. Both patients had metabolic CRs at the time of study exit.
The results from this expansion cohort of 7 patients with DHL, a cancer known to have MYC translocations, suggests that reduction of MYC expression for at least 4 hours can provide durable complete remissions lasting several years. The favorable safety profile of VIP152 allowed for long-term dosing in elderly patients with advanced disease.
A Phase 1b expansion study in MYC-driven advanced cancers is ongoing, evaluating up to 30 patients with relapsed/refractory aggressive lymphoma, and up to 40 patients with advanced solid tumors.
The poster can be accessed on the presentations section of the Vincerx website.

On June 4, 2021 GRAIL, Inc., a healthcare company whose mission is to detect cancer early,reported the first results from the interventional PATHFINDER study evaluating Galleri, a multi-cancer early detection (MCED) blood test (Press release, Grail Bio, JUN 4, 2021, View Source [SID1234583577]). The results, presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, support Galleri’s performance in clinical settings. The company also announced today that Galleri is now available in the U.S. by prescription only.

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"The interim results of PATHFINDER demonstrate that a routine blood test is capable of detecting many different cancers even before symptoms arise, an approach that has significant potential advantages," said Dr. Tomasz M. Beer, deputy director at the OHSU Knight Cancer Institute and presenting author. "Most importantly, it can detect cancers that have no recommended screening tests today, and more than two-thirds of cancers go unscreened for this reason. These results are a pivotal step toward extending early detection to many more types of cancer."

Clinical Data from PATHFINDER

PATHFINDER was designed to assess the implementation and performance of Galleri in a clinical care setting, evaluate the clinical care pathways following a "signal detected" Galleri test result, and measure the time required to achieve diagnostic resolution.

The study analyzed 6,629 individuals aged 50 years or older, an age group at elevated risk for cancer, but with no suspicion of active cancer. Compared to the general population, participants had equal or higher compliance with recommended breast and colon cancer screening tests.

In the interim analysis, an earlier version of Galleri accurately detected 29 cancers across 13 types: breast, colon or rectum, head and neck, liver and bile duct, lung, lymphoid leukemia, lymphoma, ovary, pancreas, plasma cell neoplasm, prostate, small intestine, and Waldenstrom macroglobulinemia. Of the new cancers detected, nearly 40% (9/23) were localized (stage I-II), and more than half (13/23) were detected before distant metastases (stage I-III). PATHFINDER participants will continue to be followed for 12 months, with final results expected in the first half of 2022.

"Finding cancer early, when treatment is more likely to be successful, is one of the most significant opportunities we have to reduce the burden of cancer," said Dr. Joshua Ofman, chief medical officer and head of external affairs at GRAIL. "These data suggest that, if used at scale alongside existing screening tests, the Galleri test could have a profound impact on how cancer is detected and, ultimately, on public health."

The interim PATHFINDER positive predictive value (PPV), or the likelihood that a person has cancer when a positive test result is returned, was 44.6% (95% CI: 33.2-56.7%), which is consistent with findings from GRAIL’s case-controlled Circulating Cell-free Genome Atlas (CCGA) Study.

When cancer was confirmed, Galleri’s first or second cancer signal origin prediction was 96.3% accurate (95% CI: 81.7-99.8%), with a median observed time to cancer diagnosis of 50 days. The interim analysis identified only four study-related adverse events (two related to mild anxiety before the test, one related to mild anxiety about the blood draw, and one related to mild bruising).

"Early cancer detection is critical to reducing the burden of cancer-related morbidity and mortality. These results reflect the potential real-world ability of Galleri to find deadly cancers earlier, and represent a leap forward in the effort to treat cancer more effectively," Dr. Beer said.

Data is presented by Dr. Beer, and the presentation will be available at View Source

Introducing Galleri

Galleri is now available in the U.S. by prescription only. The Galleri test is intended for use in those with an elevated risk of cancer, such as adults aged 50 or older, and as a complement to existing single cancer screening tests.

In an observational study, Galleri has demonstrated the ability to detect more than 50 types of cancer1, over 45 of which lack recommended screening tests today in the U.S., with a low false positive rate of less than 1%. When cancer is detected, Galleri can determine the cancer signal origin with high accuracy. New CCGA data published today in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), also demonstrate the ability of GRAIL’s technology to preferentially detect cancers that are more aggressive than expected based on age, and the cancer stage and type.

The blood test is supported by what is believed to be the largest clinical study program in genomic medicine, with over 140 clinical study sites, including the Mayo Clinic, Dana-Farber Cancer Institute, Cleveland Clinic, Sutter Health, OHSU, Intermountain Healthcare, and U.S. Oncology Research.

Cancer is expected to become the leading cause of death in the United States this year, in large part because the majority of cancers are found too late when outcomes are poor. Recommended screening tests save lives, but only cover five cancer types in the U.S. In fact, 71% of cancer deaths in the U.S. have no recommended early detection screening.

For more information about Galleri, visit www.galleri.com.

REFLECTION Registry

GRAIL also announced it will establish a real-world evidence study, REFLECTION, to understand the experience and clinical outcomes of 35,000 individuals in the U.S. who are prescribed the Galleri test from a healthcare provider. This follows an announcement last fall that Galleri will be offered to eligible patients in the United Kingdom (UK) later this year as part of a partnership with the UK National Health Service to support its Long Term Plan for earlier cancer diagnoses.

On June 4, 2021 Guardant Health, Inc. (Nasdaq: GH) reported that presents new data at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held from June 4-June 8, 2021, showing that its LUNAR-2 blood test is a highly sensitive test that can detect colorectal cancer (CRC) in early-stage cancer patients (Press release, Guardant Health, JUN 4, 2021, View Source [SID1234583594]). This largest ever cohort continues to demonstrate the performance and robustness of the LUNAR-2 assay.1,2

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Today, it is estimated that only 68% of adults, 50 years and older, are screened for CRC despite the Centers of Disease Control (CDC) target compliance goal of 80%.3-5 A patient-friendly blood testing option with high sensitivity could finally bridge the gap to this compliance goal, and bend the mortality curve for the second leading cause of cancer death in the U.S.6

The data (N=705) show that the LUNAR-2 assay achieved overall sensitivity of 91% in early-stage CRC (stage I, II, and III), and specificity of 94%. The performance in this new cohort of CRC cases, and cancer-free controls, is consistent with previously reported data.1-2 Notably, no differences in sensitivity for CRC detection were observed in patients presenting with asymptomatic disease, compared to those patients who were symptomatic, despite the lower cell-free DNA (cfDNA) tumor fractions observed in asymptomatic patients, suggesting the test will have clinically meaningful performance in an average-risk screening population. Further, an expanded multi-cohort analysis of over 1,300 cases of patients with CRC, demonstrated that the LUNAR-2 assay consistently delivers clinical meaningful sensitivity for the detection of early-stage cancer.

The LUNAR-2 assay achieves industry-leading performance for detecting early-stage CRC by simultaneously interrogating somatic, methylation, and fragmentomic signals from circulating tumor DNA (ctDNA) in the blood.

"It’s exciting to see the latest data on Guardant Health’s LUNAR-2 assay, which are consistent with prior data, but most importantly deliver the performance necessary for clinical adoption in average-risk colorectal cancer screening," said Jeeyun Lee, MD, Professor, Division of Hematology/Oncology, Samsung Medical Center. "It’s great to see the momentum Guardant Health has achieved since the introduction of their best-in-class liquid biopsy technology in 2014. Now, they are at the precipice of delivering a highly sensitive colorectal cancer screening test, and I look forward to seeing the outcome of their registrational study."

"What makes this data particularly exciting is that our LUNAR-2 assay continues to show clinically meaningful performance in increasingly larger cohorts of patients with early-stage cancer," said Helmy Eltoukhy, Guardant Health CEO. "Furthermore, our assay delivered comparable sensitivity in both asymptomatic and symptomatic patients, despite the significantly reduced signals in asymptomatic patients. We’re pleased with the test performance which exceeds the benchmark required for clinical adoption in an average-risk patient population."

The ECLIPSE trial, a 10,000-patient registrational study, is currently underway to evaluate the performance of LUNAR-2 to detect CRC in an average-risk adult population. If successful, Guardant Health expects data from the trial will support a premarket approval (PMA) submission to the FDA. The trial is expected to complete enrollment by the end of 2021.

On June 4, 2021 Veracyte, Inc. (Nasdaq: VCYT) reported that Medicare Administrative Contractors Palmetto GBA, WPS and CGS Administrators, LLC have finalized their coverage policies for Decipher Bladder, a genomic subtyping tool that helps physicians manage treatment decisions for patients with bladder cancer (Press release, Veracyte, JUN 4, 2021, View Source [SID1234583612]). These local coverage determinations (LCDs) make Decipher Bladder the first genomic test to be covered by Medicare for such patients. Developed through the Medicare MolDX program, the policies will become effective July 18, 2021, and provide a framework for other participating MACs to follow.

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Noridian Healthcare Solutions, another Medicare Administrative Contractor, is expected to similarly finalize its draft LCD, which will make Decipher Bladder a covered benefit for more than 62 million Medicare beneficiaries. In the United States, more than 80,000 individuals are diagnosed with bladder cancer annually, approximately 44,000 of which will have the non-metastatic, Stage I-IIIa disease indicated in these policies.

"Physicians treating patients with bladder cancer are faced with complex and potentially life-changing treatment decisions, including whether or not to prescribe neoadjuvant chemotherapy or proceed directly to radical cystectomy," said Tina Nova, Ph.D., Veracyte’s general manager, urologic cancers. "Studies have demonstrated that knowledge of an individual’s bladder-tumor molecular subtypes can help guide these decisions, over and above clinical features alone. The coverage decisions announced today will make it possible for physicians to access this critical genomic information."

The Decipher Bladder test is supported by multiple peer-reviewed clinical studies demonstrating its ability to identify which patients have a higher risk of upstaging to non-organ confined disease at surgery and which patients may benefit the most from neoadjuvant therapy. The test also can be used to identify neuroendocrine-like and immune-infiltrated subtypes, which may have implications for future therapeutic strategies.

About Decipher Bladder

Decipher Bladder is a genomic test that measures the molecular profile of bladder cancer using gene expression analysis from transurethral resected bladder tumor specimens. It was developed for bladder cancer patients with muscle-invasive disease who face the question of immediate cystectomy or systemic treatment in the neoadjuvant setting prior to cystectomy (NAC). The assay results are reported as one of five molecular subtypes (Luminal, Luminal-Infiltrated, Basal, Basal Claudin Low or Neuroendocrine-like), each of which has distinct biological composition, clinical behavior and predicted benefit from NAC.

On June 4, 2021 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported in a poster presentation preliminary data from the ongoing Phase 1/2 trial of CPI-0209, a novel, second-generation, small molecule inhibitor of Enhancer of Zeste Homolog 2 (EZH2) (Press release, Constellation Pharmaceuticals, JUN 4, 2021, View Source [SID1234583530]). These data were published online in conjunction with the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, and show comprehensive target engagement and durable exposure of CPI-0209. Anti-tumor activity of CPI-0209 in pre-clinical models was demonstrated across several advanced hematologic and solid tumor types.

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"We designed CPI-0209 to improve on first-generation EZH2 inhibitors in a number of ways, including increased potency, long residence time on target, and a lack of auto-induction of metabolism. These enhancements translate in the clinic, which we believe will be key to unlocking the full therapeutic potential of EZH2 inhibition," said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. "I am also pleased that dosing is under way in our Phase 2 expansion cohorts at the selected dose."

Preliminary Data Highlights

A total of 40 patients were treated across 14 tumor types.
A 350mg oral, once-daily dose of CPI-0209 has been selected for evaluation in Phase 2.
As of the data cut of March 9, 2021, of the 4 BAP1 loss mesothelioma patients, 1 patient had a durable partial response (PR) after four cycles of treatment and 2 had stable disease (SD). Subsequently, to the data cut, the fourth patient also had SD.
High levels of target engagement observed preclinically are now corroborated clinically.
Safety

A total of 40 patients were evaluated for safety. CPI-0209 was generally well tolerated, with a manageable adverse event profile. Across all dose cohorts, 43% of patients had at least one Grade 3 or greater treatment emergent adverse event (TEAE), 28% of patients had at least one serious adverse event (SAE). The most common TEAEs (≥ 15%) included thrombocytopenia (reversible and dose dependent), diarrhea, asthenic conditions, nausea, anemia, dysgeusia, abdominal pain and alopecia. 23% of patients reported a TEAE that led to dose reduction or interruption. Four patients discontinued treatment because of TEAEs. One patient in the highest dose cohort (375mg) experienced Grade 4 thrombocytopenia, and one patient experienced a Grade 5 adverse event due to progressive disease.

For further details, please view the ASCO (Free ASCO Whitepaper) poster.

ASCO Poster Presentation

TITLE: Phase 1/2 First-in-Human Study of CPI-0209, a Novel Small Molecule Inhibitor of Enhancer of Zeste Homolog 2 (EZH2) in Patients with Advanced Tumors (Abstract Code 3104)

About CPI-0209

CPI-0209 is a second-generation EZH2 inhibitor designed to achieve comprehensive target coverage through extended on-target residence time and enhanced potency compared with first-generation EZH2 inhibitors. These features lead to faster onset and a more comprehensive on-target action than first-generation EZH2 inhibitors, as well as robust anti-tumor activity in models of multiple hematologic and solid cancer types.

About CPI-0209 clinical trial

The Phase 1 portion of the CPI-0209 Phase1/2 clinical trial is an open label, dose escalation study in patients with advanced tumors. A total of 41 patients were enrolled, of which 40 patients received CPI-0209. The primary objective of the Phase 1 portion is to evaluate safety and determine the recommended Phase 2 dose of CPI-0209.

The Phase 2 portion is an open label, single arm study, currently enrolling 20 to 29 patients per cohort in the following tumor types: relapsed urothelial carcinoma, relapsed ovarian clear cell carcinoma, and relapsed endometrial carcinoma all with known ARID1A mutation; relapsed or refractory lymphomas; malignant pleural or peritoneal mesothelioma with known BAP1 loss; as well as metastatic castration-resistant prostate cancer. The goal of these cohorts is to establish the safety and the antitumor activity of CPI-0209 as a monotherapy for patients with these tumor types.