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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

On June 4, 2021 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug conjugates (ADCs) to treat hematological malignancies and solid tumors, reported updated clinical data from the ZYNLONTA (loncastuximab tesirine-lpyl) Phase 2 LOTIS-2 trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held virtually June 4-8, 2021 (Press release, ADC Therapeutics, JUN 4, 2021, View Source [SID1234583547]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The maturing duration of response from the ZYNLONTA Phase 2 trial reported at ASCO (Free ASCO Whitepaper) reflects the strong data set that served as the basis of the accelerated FDA approval in April," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "We are especially encouraged to see this positive trend continue to strengthen in a heavily pre-treated patient population, including patients with double- / triple-hit, advanced stage or transformed DLBCL, DLBCL refractory to first-line therapy, and patients older than 65."

In LOTIS-2, a single-arm, open-label, 145-patient Phase 2 clinical trial in patients with relapsed or refractory DLBCL who had failed ≥2 established therapies, ZYNLONTA demonstrated continued substantial antitumor activity and an acceptable safety profile. Updated results, including analysis of response in high-risk subgroups, were presented in a poster (abstract number: 7546) by Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University.

Key data at the March 1, 2021 data cut include:

Overall response rate (ORR) was 48.3% and complete response rate (CRR) was 24.8%
Median duration of response (mDoR) of 13.4 months for the 70 responders
Median duration of response not reached for patients with a complete response
Durable responses in high-risk patient groups, including:
Patients with double- / triple-hit or transformed DLBCL each had a median DoR not reached
Patients with advanced stage disease (Stage III-IV) had a median DoR of 12.6 months
Median DoR for older patients was longer than for younger patients (≥75 years, not reached; ≥65 years to <75 years, 12.6 months; <65 years, 9.3 months)
Patients with DLBCL refractory to first-line systemic therapy had a median DoR of 9.6 months compared with 12.6 months for patients who relapsed after responding to initial therapy
No new safety concerns were identified during the study and no increase in toxicity was observed in patients aged ≥65 years compared with patients <65 years
Two additional posters presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting:

Phase 3 randomized study of loncastuximab tesirine plus rituximab versus immunochemotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): LOTIS-5 (abstract number: TPS7574)
A Phase 1b, open-label, dose-escalation study to evaluate camidanlumab tesirine (Cami) as monotherapy in patients (pts) with advanced solid tumors (abstract number: 2556)
About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death. The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA approval was based on data from LOTIS-2, a large (n=145) Phase 2 multinational, single-arm clinical trial of ZYNLONTA for the treatment of adult patients with r/r DLBCL following two or more prior lines of systemic therapy. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with very difficult to treat disease, including patients with high-grade B-cell lymphoma. The trial also enrolled patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, and patients who had stem cell transplants and CAR-T therapy prior to their treatment with ZYNLONTA. Results from the trial demonstrated an overall response rate (ORR) of 48.3% (70/145 patients), which included a complete response (CR) rate of 24.1% (35/145 patients) and a partial response (PR) rate of 24.1% (35/145 patients). Patients had a median time to response of 1.3 months. At the most recent data cut-off for patients enrolled in the trial, the median duration of response (mDoR) was 13.4 months. In a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea and musculoskeletal pain. In LOTIS-2, the most common (≥10%) grade ≥3 treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), gamma-glutamyltransferase increased (17.2%) and anemia (10.3%).

ZYNLONTA is being evaluated in combination for earlier lines of therapy and as a monotherapy in other B-cell malignancies.

On June 4, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported it will host an investor and analyst video webcast event on Thursday, June 10, 2021 at 12:00 PM ET following the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, MEI Pharma, JUN 4, 2021, View Source [SID1234583563]). The event will include a review of the zandelisib program, including recent data presented at ASCO (Free ASCO Whitepaper), and commentary from key opinion leader Deepa Jagadeesh, M.D., MPH, a board-certified medical oncologist/hematologist and assistant professor, Cleveland Clinic Lerner College of Medicine, Lymphoma and Bone Marrow Transplant Program, and Taussig Cancer Institute. The event will include additional zandelisib data as well as an overview and update of MEI’s business.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Video Webcast Information
You can access the live video webcast under the investor relations section of MEI’s website on the "Events and Presentation" page at: www.meipharma.com. A replay of the video webcast will be archived for at least 30 days after the conclusion of the live event.

On June 4, 2021 Foundation Medicine, Inc. and its collaborators reported the presentation of new data analyzing the genomic landscape, comprehensive genomic profiling (CGP) utilization and treatment patterns among more than 11,000 men with advanced prostate cancer, including 12% with a predicted African genomic ancestry (Press release, Foundation Medicine, JUN 4, 2021, View Source [SID1234583578]). In what is believed to be the largest known cohort of its kind, researchers found that despite similar rates of actionable gene alterations between men of European and African ancestry, men of African ancestry were less likely to receive CGP early in their treatment course and less likely to be enrolled in clinical trials. These findings highlight the importance of additional factors, beyond inherent differences in disease biology, in potentially driving disparities in outcomes. They also underscore the need to expand access to precision medicine and clinical trial enrollment. Data will be presented during an oral presentation on June 8 at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program (ASCO21).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Prostate cancer incidence and clinical outcomes vary widely across race and ethnicity, and the underlying drivers of these outcomes are multifactorial, including systemic barriers that lead to differences in access to genomic and precision medicine. Men of African ancestry are particularly underrepresented in prostate cancer research. With this study, Foundation Medicine and collaborators at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, the University of Michigan and Harvard Medical School explored the interplay between ancestry and patient care.

"Men of African ancestry experience the greatest burden of disease in prostate cancer, and this research indicates that differences in cancer care are not solely based on biological factors, but rather points to socioeconomic factors such as access to comprehensive genomic profiling and clinical trial enrollment," said study investigator Brandon Mahal, M.D., Assistant Professor, Radiation Oncology and Assistant Director of Community Outreach and Engagement, Sylvester Comprehensive Cancer Center. "To ensure equitable opportunities for precision medicine, we need to expand access to and awareness of advances that impact patient care and outcomes, including timely use of genomic testing to help make informed treatment decisions."

The study analyzed 11,741 men with advanced prostate cancer who received CGP as part of routine clinical care, along with a subset of 897 patients with real-world clinical data from Foundation Medicine and Flatiron Health’s joint clinico-genomic database (CGDB). Results showed that the rates of genomic alterations were largely similar across ancestry, including alterations in BRCA1/2, androgen receptor, DNA damage response pathway genes and actionable genes with therapy implications. Within the CGDB cohort, the proportion of patients receiving immunotherapy and PARP inhibitors was also similar across ancestry. However, men of African ancestry were less likely to receive a clinical study drug than men of European ancestry (11% vs. 30%). Further, men of African ancestry received a median of two lines of therapy prior to CGP, compared to one line of therapy for men of European ancestry, highlighting the extended time from diagnosis to implementation of precision medicine. These factors may potentially impact the genomic landscape, outcomes, and ultimately disparities.

"At Foundation Medicine, we strive to better understand barriers at different stages of a patient’s journey and identify opportunities to mitigate disparities in cancer care. Our study highlights the need for the cancer community to understand and systematically define barriers to care across different populations, especially those traditionally underrepresented in clinical research," said study co-lead Smruthy Sivakumar, PhD, scientist at Foundation Medicine. "The results contribute to our knowledge of comprehensive genomic profiling and real-world data to better understand the barriers patients face in accessing quality cancer care – a critical step toward addressing persistent disparities," added Jessica Lee, study co-lead and scientist at Foundation Medicine.

A full list of research being presented by Foundation Medicine and its collaborators at ASCO (Free ASCO Whitepaper)21 can be found at www.foundationmedicine.com/event/asco2021.

On June 4, 2021 Tachyon Therapeutics, Inc. ("Tachyon" or "the Company"), a research and development biotechnology company, reported two abstract presentations of the Company’s lead product candidate, TACH101, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting. ASCO (Free ASCO Whitepaper) is being held virtually from June 4-8, 2021 (Press release, Tachyon Therapeutics, JUN 4, 2021, View Source [SID1234583596]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited about the emerging preclinical profile of TACH101, the first inhibitor of KDM4 histone demethylase to be in clinical studies," stated Frank Perabo, MD, PhD, CEO of Tachyon Therapeutics. "Epigenetic processes play a fundamental role in regulation of cellular biology, but when unregulated, can lead to cancer development and progression. Data presented at ASCO (Free ASCO Whitepaper) show favorable pharmacologic properties for TACH101, compelling efficacy data in animal models, and broad applicability as a potential anti-cancer agent. We look forward to advancing this molecule into first-in-human trials later this year."

Highlights from the two ASCO (Free ASCO Whitepaper) abstracts are summarized below:

Abstract #3105

TACH101 demonstrated potent increase in H3 methylation levels (H3K36me3), showing on-target activity.
TACH101 triggered effective tumor control in xenograft models including colorectal, esophageal, gastric, breast, and lymphoma with tumor growth inhibition of up to 100%.
Further evaluation using a panel of patient-derived colorectal models and patient-derived organoids showed a strong correlation of TACH101 sensitivity with MSI-H status (IC50 ranges 1-150 nM).
TACH101 reduced tumorigenic potential by 4.4-fold, suggesting that reduction of cancer stem cells by TACH101 may be effective in therapy-resistant settings.
The poster presentation of Abstract #3105 is available for viewing on the ASCO (Free ASCO Whitepaper) Annual Meeting website at View Source

Abstract #e15067

TACH101 showed potent KDM4 inhibition without significant off-target activity in in vitro and in vivo studies.
Pharmacokinetic studies showed TACH101 exhibited low clearance, moderate volume of distribution, and good oral bioavailability in mouse, rat, and dog.
TACH101 had little or no inhibitory effects on CYP enzyme activities.
The exposure from oral administration in rats and dogs was dose proportional and was not affected by food intake in dogs.
Presentation of Abstract #e15067 is available for viewing on the ASCO (Free ASCO Whitepaper) Annual Meeting website at View Source