On June 4, 2021 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a commercial-stage biopharmaceutical company developing innovative medicines to improve the lives of people with cancer, reported two e-poster presentations at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Deciphera Pharmaceuticals, JUN 4, 2021, View Source [SID1234583503]). The presentations include intra-patient dose escalation (IPDE) data from the INVICTUS Phase 3 study of QINLOCK in patients with advanced gastrointestinal stromal tumor (GIST), as well as preliminary results from the Company’s ongoing Phase 1b/2 study of rebastinib in combination with paclitaxel in patients with endometrial cancer.

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Both e-poster presentations are now available on-demand via the ASCO (Free ASCO Whitepaper) Meeting Library and on the Company’s website at www.deciphera.com/presentations-publications.

"We are committed to understanding the full benefit QINLOCK may provide to patients with GIST and the data presented at ASCO (Free ASCO Whitepaper) further demonstrate the important clinical benefits QINLOCK can provide in this population," said Matthew L. Sherman, MD, Executive Vice President and Chief Medical Officer of Deciphera. "Importantly, consistent with our Phase 1 data, these exploratory results from the Phase 3 study show that dose escalation to QINLOCK 150 mg BID after disease progression on QINLOCK 150 mg QD can offer substantial additional clinical benefit with a tolerable safety profile. As the body of data supporting QINLOCK’s efficacy and safety continues to grow, we are pleased with QINLOCK’s potential to offer clinically meaningful benefit for GIST patients in multiple settings of the disease."

Dr. Sherman continued, "Results presented today from the endometrial cancer cohort of the Phase 1b/2 study of rebastinib, our selective TIE2 inhibitor, in combination with paclitaxel continue to demonstrate rebastinib’s anti-tumor activity as well as its evolving safety profile. We look forward to sharing updated data from the platinum-resistant ovarian cancer cohort of this study in the third quarter of 2021 and finalizing the pivotal development plan for rebastinib in combination with paclitaxel in the second half of 2021."

INVICTUS Dose Escalation Data

The INVICTUS Phase 3 clinical study is a randomized (2:1), double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of QINLOCK compared to placebo in patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. The Company previously reported primary results from the randomized portion of the INVICTUS study, in which QINLOCK significantly improved PFS and showed a clinically meaningful overall survival (OS) benefit. An exploratory analysis was conducted to assess the safety and efficacy of QINLOCK dose escalation to 150 mg BID among patients randomized to QINLOCK 150 mg QD in the INVICTUS study.

As of an August 10, 2020 cutoff date, of the 85 patients randomized to QINLOCK 150 mg QD in the INVICTUS study, 43 dose escalated to 150 mg BID after disease progression by blinded independent central review using modified RECIST version 1.1.

Among the 43 patients in the QINLOCK arm who dose escalated, initial median PFS, or mPFS1, was 4.6 months (95% CI 2.7–6.4) and the subsequent median PFS, or mPFS2, from the day of dose escalation to second disease progression or death was 3.7 months (95% CI 3.1–5.3). The ratio of mPFS2/mPFS1 was 80%.
Median OS was 18.4 months in patients randomized to QINLOCK 150 mg QD with progressive disease and who dose escalated to 150 mg BID (n=43) and 14.2 months in those randomized to QINLOCK 150 mg QD with progressive disease and not dose escalating (n=22) (HR 0.74, 95% CI 0.37–1.49).
QINLOCK 150 mg BID was well tolerated with a similar safety profile to QINLOCK 150 mg QD, with new or worsening Grade 3–4 TEAEs of anemia in 6 (14%) and abdominal pain in 3 (7%) patients.
Updated Preliminary Data from the Ongoing Phase 1b/2 Study of Rebastinib in Combination with Paclitaxel in Endometrial Cancer

The Phase 1b/2 study of rebastinib in combination with paclitaxel is a two-part, open-label, multicenter study assessing the safety, tolerability, anti-tumor activity, and pharmacokinetics of rebastinib in patients with advanced or metastatic solid tumors. As previously announced, both the endometrial and platinum-resistant ovarian cancer cohorts in Part 2 of the study advanced into the second stage of the Simon two-stage design based on demonstrating at least five responses in each cohort.

As of a March 19, 2021 cutoff date, 38 patients with endometrial cancer initiated treatment with rebastinib in combination with weekly paclitaxel 80 mg/m2. All 38 patients received prior taxane, with 44% of patients having received four or more prior anti-cancer regimens, with a median of three prior therapies across all patients. 16 patients were treated with rebastinib at a starting dose of 100 mg BID (11 reduced to 50 mg BID) and 22 patients were treated with a starting dose of 50 mg BID. Of the 38 patients with endometrial cancer who initiated treatment with rebastinib, the median duration of treatment was 3.7 months.

Of the 33 patients in the modified intent-to-treat (mITT) population:

There were 11 partial responses (8 confirmed) and 12 patients with stable disease for an objective response rate of 33% (unconfirmed and confirmed) and 24% (confirmed only) with a median duration of response of 7.4 months,
The median progression-free survival (PFS) was 6.2 months.
The majority of the common (≥15%) treatment-emergent adverse events (TEAEs) were Grade 2 or lower.
Nine patients experienced SAEs at least possibly related to rebastinib including muscular weakness (n=3), nausea (n=2), acute myocardial infarction (n=1), atrial flutter (n=1), dehydration (n=1), noninfective encephalitis (n=1), peritonsillitis (n=1), and stress cardiomyopathy (n=1).
The Company expects to present updated data from the ongoing Phase 1b/2 study of rebastinib in combination with paclitaxel in the platinum-resistant ovarian cancer cohort in the third quarter of 2021 and finalize the pivotal development plan for rebastinib in combination with paclitaxel in the second half of 2021, subject to favorable data and discussions with regulators.

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 [SID1234583522]).

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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 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported clinical data for lifileucel in combination with pembrolizumab in patients with advanced melanoma (Press release, Iovance Biotherapeutics, JUN 4, 2021, View Source [SID1234583538]). The data are now available in an ePoster at the ASCO (Free ASCO Whitepaper) 2021 Annual Meeting.

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Antonio Jimeno M.D., Ph.D., Professor of Medicine/Oncology and Otolaryngology at the University of Colorado School of Medicine stated, "Anti-PD-1 therapy has become standard of care in frontline melanoma, yet we are still looking for ways to help more patients respond and to improve upon the depth and durability of responses. The 86% Overall Response Rate (ORR) for lifileucel in combination with pembrolizumab is remarkable and suggests a potential additive effect for early-line treatment of patients with melanoma. I look forward to investigating this treatment approach in additional patients with melanoma as well as in other tumor types such as head and neck squamous cancer."

Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, "We are very pleased with the initial efficacy and safety results for lifileucel in combination with pembrolizumab in patients who are naïve to anti-PD-1 therapy. We are particularly impressed by the complete response observations and noted conversion of several partial to complete responses over time. These data in melanoma also build upon our initial data for TIL in combination with pembrolizumab in head and neck cancer, supporting the broader potential for TIL in earlier anti-PD-1 naïve treatment settings across indications."

Early data suggest the response rate of lifileucel plus pembrolizumab may be additive and confirm the potential feasibility and activity of this combination in patients with immune checkpoint inhibitor (ICI)-naïve advanced melanoma. Cohort 1A in the IOV-COM-202 study is evaluating lifileucel in combination with pembrolizumab in patients who are naïve to ICI, or anti-PD-1, therapy. Initial patients (n=7) enrolled in Cohort 1A had high tumor burden at baseline, and 71.4% had not received any prior systemic therapy.

Six of the seven patients had a confirmed objective response, representing an 86% ORR (2 complete responses (CR), 1 unconfirmed CR (uCR) who had not yet reached the confirmatory CR assessment, and 3 partial responses (PR)), with one best response of stable disease. Responses deepened over time and the CR/uCR rate was 43%. Poster data extraction was in April 2021 and the median follow up was 8.2 months. ORR was investigator-assessed per RECIST 1.1. In a subsequent data cut in May 2021, all ongoing responses continued.

The Cohort 1A results also demonstrated that lifileucel can be safely combined with pembrolizumab. The treatment-emergent adverse event (TEAE) profile was consistent with the underlying disease and known adverse event (AE) profiles of pembrolizumab, non-myeloablative lymphodepletion (NMA-LD) and IL-2. The median number of doses of IL-2 and pembrolizumab were six and 10, respectively.

Iovance Poster at ASCO (Free ASCO Whitepaper) 2021
Title: Safety and efficacy of lifileucel (LN-144), an autologous, tumor infiltrating lymphocyte cell therapy in combination with pembrolizumab for immune checkpoint inhibitor naïve patients with advanced melanoma.
Authors: Sajeve Samuel Thomas, et al.
Session Title: Melanoma/Skin Cancers
Session Type: ePoster Session
Abstract Number: 9537
Location: ASCO (Free ASCO Whitepaper) Meeting Library at View Source and View Source
ePoster Viewing: on demand beginning Friday, June 4, 2021 at 9:00 a.m. ET
Webcast and Conference Call
Iovance will host a webcast and conference call on Sunday, June 6, at 12:00 p.m. ET to discuss ASCO (Free ASCO Whitepaper) clinical data updates for lifileucel alone and in combination with pembrolizumab in patients with advanced melanoma. Iovance senior leadership, together with Dr. Omid Hamid of The Angeles Clinic, will present a summary of the ASCO (Free ASCO Whitepaper) data from Cohort 1A in the IOV-COM-202 study as well as the upcoming oral presentation of updated Cohort 2 data from the C-144-01 clinical study.

The conference call dial-in numbers are 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and the access code is 4858337. The live webcast can be accessed in the Investors section of the company’s website at View Source The archived webcast will be available for a year in the Investors section at www.iovance.com.

On June 4, 2021 Amgen (NASDAQ:AMGN) reported that it will present at the Goldman Sachs 42nd Annual Global Healthcare Conference at 4:40 p.m. ET on Wednesday, June 9, 2021 (Press release, Amgen, JUN 4, 2021, View Source [SID1234583555]). David M. Reese, M.D., executive vice president of Research and Development and Peter H. Griffith, executive vice president and chief financial officer at Amgen will present at the conference. Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

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The webcast, as with other selected presentations regarding developments in Amgen’s business given at certain investor and medical conferences, can be accessed on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

On June 4, 2021 Sanofi reported that it is partnering with leading groups delivering practice-changing breast cancer research, the Breast International Group (BIG), the European Organization for Research and Treatment of Cancer (EORTC) and the Alliance Foundation Trials (AFT), to initiate a pivotal trial of an oral selective estrogen receptor degrader (SERD) in the adjuvant setting (Press release, Sanofi, JUN 4, 2021, View Source [SID1234583518]). The Phase 3 AMEERA-6 study will evaluate the efficacy and safety of Sanofi’s amcenestrant vs tamoxifen for women with estrogen receptor-positive (ER+) breast cancer who were unable to continue their adjuvant aromatase inhibitor (AI) therapy.

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"Together with our research partners, BIG conducts landmark, practice-changing trials that can have a significant impact on the lives of women with breast cancer," said David Cameron, Chair of the BIG Executive Board. "Adjuvant therapy helps prevent and delay the progression of disease into the later setting. However, current adjuvant therapies, like AIs, can have side effects for some women, which may cause them to discontinue the medication prematurely. Amcenestrant may be a potential option for women in this setting and we look forward to working with Sanofi, EORTC and AFT to investigate this further."

"We look forward to collaborating with these leading academic networks to investigate amcenestrant in the adjuvant setting through AMEERA-6. Based on encouraging data emerging from our ongoing clinical program, we believe that amcenestrant, an investigational oral SERD, has the potential to become a best-in-class oral endocrine backbone therapy," said Peter Adamson, M.D., Global Development Head, Oncology at Sanofi. "Additional treatment options for patients with breast cancer are needed to allow women to remain on adjuvant therapy and decrease their risk of progressive disease."

Amcenestrant is an oral SERD that antagonizes and degrades the estrogen receptor (ER), resulting in inhibition of the ER signaling pathway. Amcenestrant is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority.

Despite the established clinical efficacy of tamoxifen and AIs in early breast cancer, many patients experience disease recurrence because of resistance to therapy, non-adherence or premature discontinuation of their adjuvant therapy.1 Additional treatment options in the adjuvant setting in early breast cancer are needed to prevent women from developing advanced, incurable disease and could represent a significant treatment advance.

As per the terms of the Pre-Study Agreement, Sanofi will be the sponsor and will provide funding and investigational drug product for the global study. BIG will conduct the study within the BIG network, EORTC will oversee study management and data analysis, as well as the medical management, and AFT will conduct the United States portion of the study. Sanofi will conduct this global study in selected countries outside the geographical scope of the academic networks, as further described in a follow-on agreement under negotiation among the four parties. The protocol is being developed in collaboration with all four parties, including AFT, BIG, EORTC and Sanofi.