On June 4, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data on its investigational CD20xCD3 T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, and its first-in-class anti-CD79b antibody-drug conjugate, Polivy (polatuzumab vedotin), in non-Hodgkin lymphoma (NHL) will be presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting from 4-8 June 2021 (Press release, Hoffmann-La Roche, JUN 4, 2021, View Source [SID1234583565]).

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"People with difficult-to-treat blood cancers such as non-Hodgkin lymphoma still need more options to help improve outcomes," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We are encouraged by promising data from our emerging T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, and the antibody-drug conjugate, Polivy, that demonstrate the potential of these novel immunotherapeutic approaches for various groups of patients."

While approximately 500,000 people worldwide are diagnosed with NHL each year, treatment options are currently limited and resistance to existing therapies or relapse following treatment is common.1 The most prevalent form of NHL, accounting for about 40% of newly diagnosed NHL cases, is an aggressive form called diffuse large B-cell lymphoma (DLBCL), that comes with a life expectancy of weeks or months if left untreated.2,3

In clinical trials to date, the investigational CD20xCD3 T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, have shown promising responses across multiple types of NHL, including relapsed or refractory (R/R) DLBCL and follicular lymphoma (FL). Pivotal data for these medicines are expected this year and Roche is targeting a regulatory filing for mosunetuzumab in FL by the end of 2021, following its U.S. Food and Drug Administration Breakthrough Therapy Designation granted in June 2020. Key data on mosunetuzumab and glofitamab to be presented at the meeting include:

Phase I NP30179 study investigating step-up dosing of glofitamab in heavily pre-treated R/R NHL, showed high, ongoing complete responses (CRs) and an acceptable safety profile. After a median follow-up of 6.3 months, results showed that glofitamab achieved a complete metabolic response rate, defined as the disappearance of metabolic tumour activity, of 71.4% in patients with aggressive (fast-growing) NHL. The most common adverse events (AEs) were cytokine release syndrome (CRS) (63.5%), neutropenia (38.5%), and pyrexia (32.7%); CRS events were mostly low grade and confined to the first cycle of treatment.4
Phase I/II GO40516 study of mosunetuzumab in combination with Polivy in R/R NHL showed promising efficacy and an acceptable safety profile. The regimen achieved a CR of 54.5% in all patients. Eighty six percent of patients evaluated had aggressive NHL, and these patients achieved a CR rate of 47.4%. The most frequent treatment-related AEs were neutropenia (45.4%), fatigue, nausea, and diarrhoea (all 36.4%) and CRS (9.1%; all Grade 1).5
Broad development programmes are ongoing for mosunetuzumab and glofitamab, including the phase III GO42909 trial investigating mosunetuzumab plus lenalidomide versus MabThera/Rituxan (rituximab) plus lenalidomide in R/R FL, which will soon be enrolling patients. For glofitamab, the phase III GO41944 open-label, randomised trial designed to evaluate the safety and efficacy of glofitamab plus gemcitabine and oxaliplatin (glofit-GemOx) versus MabThera/Rituxan plus GemOx in patients with R/R DLBCL, is also ongoing.

Roche is committed to pursuing treatment solutions that can be tailored to meet the various needs of both people living with NHL and healthcare professionals. Polivy is already a treatment option for people with R/R DLBCL and continues to show potential in multiple combinations. Key data at the meeting include:

New triplet combination of Polivy with MabThera/Rituxan and lenalidomide, which demonstrated promising activity in difficult-to-treat R/R DLBCL, based on results from the phase Ib/II GO29834 study. With a median follow-up of 9.7 months, median overall survival was 10.9 months (95% CI: 7.4–NE) and median progression-free survival was 6.3 months (95% CI: 4.5–9.7) in patients treated with the triplet. The most commonly reported Grade 3-4 AEs were neutropenia (58.0%), thrombocytopenia (14.0%), infections (14.0%) and anaemia (11.0%).6

As a leader in haematology development, Roche will continue to follow the science to expand and improve upon treatment options for healthcare providers and people with difficult-to-treat blood cancers.

Keep up to date with ASCO (Free ASCO Whitepaper) news and updates by using the hashtag #ASCO21 and follow Roche on Twitter via @Roche and on LinkedIn.

About Roche’s investigational bispecifics in haematology
Roche is currently developing two T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Mosunetuzumab and glofitamab differ in their structures, and both are being developed by Roche as part of our ongoing strategy to explore multiple bispecific formats, to identify those that maximise potential clinical benefits for patients. Mosunetuzumab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions, but is different from naturally-occurring antibodies in that one ‘Fab’ region targets CD20 and the other ‘Fab’ region targets CD3. Glofitamab is based on a novel structural format called ‘2:1’, which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions which bind to CD20, and one ‘Fab’ region which binds to CD3. The clinical development programmes for mosunetuzumab and glofitamab include ongoing investigations of these molecules as monotherapies and in combination with other medicines, for the treatment of people with CD20-positive B-cell non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

About Polivy (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of NHL, making it a promising target for the development of new therapies.7,8 Polivy binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.9,10 Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL. Polivy is marketed in the US by Genentech as Polivy (polatuzumab vedotin-piiq), with piiq as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/Ib, multicentre, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of glofitamab. In this study, glofitamab is assessed as a single-agent and in combination with Gazyva/Gazyvaro (obinutuzumab), following pre-treatment with a one-time, fixed-dose of Gazyva/Gazyvaro, in people with relapsed or refractory (R/R) B-cell NHL. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose and tolerability.

About the GO40516 study
The GO40516 study [NCT03671018] is a phase I/II, multicentre, open-label study, evaluating the efficacy, safety, tolerability and pharmacokinetics of mosunetuzumab in combination with Polivy in people with B-cell NHL. It consists of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with R/R DLBCL and 2L+ R/R FL. Outcome measures include best overall response rate, maximum tolerated dose and tolerability.

About the GO29834 study
The GO29834 study [NCT02600897] is a phase Ib/II, multicentre, open-label study, evaluating the efficacy and safety of Polivy with MabThera /Rituxan (rituximab) and lenalidomide in R/R DLBCL. Outcome measures include complete response and tolerability.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan, Gazyva/Gazyvaro, Polivy, Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, and cevostamab, targeting FcRH5 and CD3; Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On June 4, 2021 Novartis reported that results from the pivotal Phase III RATIONALE 302 trial showing the investigational anti-PD-1 immune checkpoint inhibitor tislelizumab improved overall survival (OS) versus chemotherapy (median 8.6 months vs. 6.3 months, p=0.0001) (Press release, Novartis, JUN 4, 2021, View Source [SID1234583564]).1 The study evaluated tislelizumab in patients with unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who had received prior systemic therapy. Results were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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Results from RATIONALE 302 in ESCC showed tislelizumab extended median OS by 2.3 months compared to chemotherapy with a 30% reduction in the risk of death (HR=0.70, 95% CI: 0.57-0.85, p=0.0001).1 In PD-L1 positive patients, tislelizumab extended median OS by 3.5 months with a 46% reduction in the risk of death (HR=0.54, 95% CI: 0.36-0.79, p=0.0006).1

"These data show that tislelizumab has the potential to help patients with esophageal squamous cell carcinoma – one of the deadliest types of cancers – live longer," said Jeff Legos, Ph.D., MBA, Senior Vice President and Head of Oncology Drug Development. "We are excited about these results from the newest asset in our portfolio of transformational medicines and look forward to sharing these data with regulatory authorities, as we continue to explore the full potential of this uniquely designed anti-PD-1 antibody."

Treatment with tislelizumab demonstrated median progression-free survival (PFS) of 1.6 months compared to 2.1 months (HR=0.83, 95% CI: 0.67–1.01). Tislelizumab demonstrated a higher and more durable anti-tumor activity than chemotherapy (objective response rate [ORR], 20.3% vs. 9.8%; median duration of response [DoR], 7.1 months vs. 4.0 months).1

The discontinuation rate due to treatment-related adverse events (TRAEs) was lower in patients who received tislelizumab (6.7%) compared to chemotherapy (13.8%). The most common all-grade TRAEs (≥10%) with tislelizumab were increased aspartate aminotransferase (11.4%), anemia (11%) and hypothyroidism (10.2%). No new safety signals were identified.1

"Most patients with this type of esophageal cancer are diagnosed with advanced disease, resulting in a poor prognosis for this difficult-to-treat cancer," said Jaffer Ajani, M.D., professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. "The impact tislelizumab had on survival compared to chemotherapy in this study is highly meaningful and encouraging news for patients, caregivers and treating oncologists."

Esophageal squamous cell carcinoma is the most common type of esophageal cancer globally and the sixth leading cause of cancer-related death worldwide.3 Each year, esophageal cancer claims nearly as many lives as colon cancer across the globe.3 More than two-thirds of patients with ESCC have advanced or metastatic disease at the time of diagnosis.4 The average five-year survival rate is only five percent.5

RATIONALE 302 is a randomized, global Phase III study assessing tislelizumab versus chemotherapy in patients with advanced unresectable/metastatic ESCC after prior systemic therapy. The primary endpoint is OS in the intent-to-treat (ITT) population. The key secondary endpoint is OS in PD-L1 positive patients (vCPS ≥10%). Additional secondary endpoints included PFS, ORR, DoR and safety endpoints.1

Data on tislelizumab in MSI-H cancers presented
The RATIONALE 209 study reported that tislelizumab showed durable anti-tumor activity in patients with previously treated, locally advanced, unresectable or metastatic microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) cancers, which are known to be more responsive to immune checkpoint modulation. Treatment with tislelizumab demonstrated an ORR of 45.9% among all tumor types, including four complete responses (CR) and 30 partial responses (PR). No disease progression was reported in the 34 responders (CR + PR), with a 12-month DoR rate of 100%).2

Five percent of patients treated with tislelizumab discontinued treatment due to TRAEs, and no new safety signals were identified. Grade ≥3 TRAEs occurred in 42.5% of patients.2

MSI-H cancer cells have a defect in the ability to correct mistakes that occur when DNA is copied, leading to mutations that contribute to cancerous growth. Many types of cancer may have a high level of microsatellite instability, but it is seen most often in CRC, gastric cancer and endometrial cancer.6

RATIONALE 209 is a single-arm, open-label Phase II study evaluating the efficacy and safety of tislelizumab monotherapy in adult patients with previously treated, locally advanced, unresectable or metastatic histologically confirmed MSI-H/dMMR solid tumors. Radiological imaging was performed at nine weeks, then every six weeks for the first year of therapy and every 12 weeks thereafter. The primary endpoint was IRC-assessed ORR. Secondary endpoints included time to response, DoR, disease control rate, PFS, OS and safety.2

Visit View Source for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO (Free ASCO Whitepaper)21 Virtual Scientific Program data presentations (for registered participants).

About tislelizumab
Tislelizumab was specifically engineered to minimize binding to macrophage Fcγ receptors, a potential mechanism of anti–PD-1 resistance.7 Tislelizumab is an important component of Novartis’s immuno-oncology strategy – one of four bold approaches to reimagining cancer and transforming patients’ lives.

In an agreement finalized earlier this year, BeiGene granted Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan through a collaboration and license agreement.

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.

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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 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 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported positive in vivo data that provide further evidence on the utility of its INTASYL self-delivering RNAi therapy platform in the field of immuno-oncology (Press release, Phio Pharmaceuticals, JUN 4, 2021, View Source [SID1234583561]). The new study data show how INTASYL can be easily deployed to target multiple proteins and provide evidence of the synergy of the Company’s pipeline products. In the study, INTASYL specifically dual-targeting BRD4 and PD-1 elicited complete tumor responses in an in vivo hepatoma model, and significantly outperformed the efficacy of small molecule and antibody treatments towards the same targets.

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In this study, the Company assessed the efficacy of mouse/human BRD4-targeting INTASYL PH-894 as monotherapy or co-formulated with mouse PD-1 targeting INTASYL mPH-762, in treating a subcutaneous Hepa1-6 model of murine hepatoma in C57BL/6N mice. Positive controls included JQ-1, a small molecule inhibitor of BRD4 and anti-mouse PD-1 monoclonal antibody (mAb) or both treatments.

"We are excited by these new in vivo study results presented at ASCO (Free ASCO Whitepaper) today, which highlight the potential of INTASYL as a mono- or dual-targeting therapy platform. By using doses that were well below the optimal single agent therapeutic dose identified in previous animal studies, we can obtain very high efficacy by dual-targeting BRD4 and PD-1. Even at these suboptimal concentrations, the dual-targeting INTASYL compound elicited complete responses in 83% of mice, and outperforming JQ-1 and anti-PD-1 mAb treatments, either used individually or in combination. Data from the study also suggests that the dual targeting INTASYL treatment resulted in a superior safety profile, as compared to the JQ-1 and anti-PD-1 mAb treatments," stated Dr. Simon Fricker, Phio’s VP of Research. He added, "These data further support our message that INTASYL can outperform other therapeutic approaches, and that synergistic drug combination approaches can be easily executed with a single INTASYL formulation."

A poster further detailing the data presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting titled "INTASYL self-delivering RNAi therapy specifically dual-targeting BRD4 and PD-1 elicits complete tumor responses and evidence of synergy in a subcutaneous Hepa1-6 model of murine hepatoma in C57BL/6N mice" will be made available on the "Investors – Events and Presentations" section of the Company’s website (click here).