On December 19, 2022 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported positive results from the fourth interim analysis of the ARC-7 study in patients with first-line, metastatic non-small cell lung cancer (NSCLC) with PD-L1 tumor proportion score (TPS) ≥50% without epidermal growth factor receptor or anaplastic lymphoma kinase (EGFR/ALK) mutations. ARC-7 is a Phase 2, multicenter, three-arm, randomized, open-label study evaluating the combinations of Fc-silent anti-TIGIT monoclonal antibody domvanalimab plus anti-PD1 monoclonal antibody zimberelimab (doublet) and domvanalimab plus zimberelimab and etrumadenant, an A2a/b adenosine receptor antagonist (triplet), versus zimberelimab monotherapy. These results will be presented tomorrow during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Monthly Plenary Series,a new, virtual forum for presentation and discussion of the latest cancer research.

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"It is particularly encouraging to see that combination treatments may offer potentially meaningful advances for people with non-small cell lung cancer based on the largest, prospectively randomized Phase 2 study of anti-TIGIT and anti-PD1 antibodies to date," said Melissa L. Johnson, M.D., Director, Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, and Lead Investigator for the ARC-7 study. "The preliminary improvements observed for each of the doublet and triplet regimens across multiple efficacy measures reinforce our confidence in the potential therapeutic benefit of inhibiting the TIGIT pathway and provide further support for the ongoing Phase 3 studies."

At the time of data cutoff, efficacy was evaluated in patients who had at least 13 weeks of follow-up and were therefore potentially eligible for at least two imaging scans (n=133), and safety was evaluated in all enrolled patients (n=149). With a median follow-up time for efficacy duration of approximately 12 months, both the doublet and triplet combinations demonstrated clinically meaningful improvements in median progression-free survival (PFS) and six-month landmark PFS rates compared to zimberelimab monotherapy, with a 45% reduction in risk of disease progression or death for the doublet and 35% for the triplet.

Each of the domvanalimab-containing study arms also demonstrated clinically meaningful improvements in objective response rate (ORR) compared to zimberelimab monotherapy. Confirmed ORR was 27%, 41% and 40% for the zimberelimab monotherapy arm and the domvanalimab-doublet and -triplet arms, respectively. While the triplet arm did not show an improvement over the doublet arm, it reinforces the results observed in the doublet arm, and the study will continue to monitor PFS, as well as overall survival, for the triplet arm as these data mature.

The efficacy results including ORR and PFS are summarized in the table below:

Endpoint

zimberelimab (Z)
monotherapy

(n=44)

domvanalimab +
zimberelimab (DZ)

(n=44)

etrumadenant +
domvanalimab +
zimberelimab (EDZ) (n=45)

Progression-free Survival (PFS)

Median in Months (95% CI)

5.4 (1.8, 9.6)

12.0 (5.5, NE)

10.9 (4.8, NE)

Hazard Ratio* (95% CI)

0.55 (0.31, 1.0)

0.65 (0.37, 1.1)

Six-month PFS rate (95% CI)

43% (27, 59)

65% (49, 80)

63% (48, 78)

Objective Response Rate (ORR)

ORR+ (95% CI)

27% (15.0, 42.8)

41% (26.3, 56.8)

40% (25.7, 55.7)

*Hazard ratio is for comparing domvanalimab-containing study arms to zimberelimab monotherapy.

+ Based on confirmed response per RECIST 1.1

NE=not evaluable
"Results from this randomized and controlled Phase 2 trial in a large number of patients validate the potential for an anti-TIGIT/anti-PD1 combination to improve outcomes for patients with metastatic NSCLC," said Dimitry S.A. Nuyten, M.D., Ph.D., Chief Medical Officer of Arcus Biosciences. "Arcus has been at the forefront of developing differentiated combination therapies, and these data are important for patients in need of potential new options, the oncology community’s understanding of TIGIT and for Arcus as a leader in the discovery and development of innovative therapeutics."

"As these data mature, we continue to see meaningful differentiation with domvanalimab across several measures of efficacy," said Bill Grossman, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Gilead Oncology. "These results reinforce the potential opportunity for anti-TIGIT treatments to provide benefit for people with lung cancer and other challenging tumors. We remain committed to accelerating our joint development program with Arcus across our four registrational Phase 3 studies."

No unexpected safety signals were observed across the three study arms at the time of data cutoff. The domvanalimab-containing study arms appeared to be generally well tolerated and showed an overall safety profile consistent with the known safety profiles of each individual molecule to date. Grade ≥3 treatment-emergent adverse events occurred in 58% of participants in the zimberelimab monotherapy study arm, 47% of the doublet arm, and 52% of the triplet arm. Incidence of infusion-related reactions was low across all treatment arms: 4%, 4% and 10% for zimberelimab monotherapy and the domvanalimab-doublet and -triplet arms, respectively. Immune-related adverse events, including the incidences and grades of rash and pruritus, were generally low and manageable with topical corticosteroids.

This interim analysis was conducted as of the clinical data cutoff date of August 31, 2022, with a total of 150 patients randomized across the three study arms. Patients in the study will continue to receive treatment per protocol, and an updated analysis including efficacy evaluation for all 150 patients is expected to be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2023. The protocol-specified primary PFS analysis will be conducted later in 2023 once a specified number of events are achieved.

Domvanalimab, zimberelimab and etrumadenant are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use globally, and their safety and efficacy for the treatment of lung cancer have not been established.

Webinar

At 5:00 p.m. Eastern Time / 2:00 p.m. Pacific Time on Tuesday, December 20, 2022, Gilead and Arcus executives will co-host a webinar to discuss the ARC-7 Plenary findings. The live webcast can be accessed via the Investor link on www.gilead.com or on www.arcusbio.com. The webinar will be archived for at least 30 days following the presentation.

About the ARC-7 Study

The ARC-7 study is a Phase 2, multicenter, three-arm, randomized, open-label study evaluating the safety and efficacy of anti-TIGIT antibody domvanalimab plus anti-PD1 antibody zimberelimab (doublet) versus domvanalimab plus zimberelimab and etrumadenant (triplet), an A2a/b adenosine receptor antagonist, versus zimberelimab monotherapy in 150 patients with first-line metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥50% and no EGFR or ALK mutations. Patients are randomized 1:1:1 across the three study arms, and patients who progress on zimberelimab monotherapy may cross over to receive the triplet. At the time of this interim analysis, 133 patients had at least 13 weeks of follow-up (potentially eligible for at least two tumor assessments). The co-primary endpoints are objective response rate and progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Secondary endpoints include duration of response, disease control rate, overall survival and safety. ARC-7 is a proof of concept study to assess the safety and efficacy of domvanalimab-containing study arms over zimberelimab monotherapy. More information about ARC-7 is available at: View Source

About Domvanalimab

Domvanalimab is an Fc-silent investigational monoclonal antibody that is designed to bind to TIGIT, a protein receptor on immune cells that acts as a brake on the immune response. Cancer cells can exploit TIGIT to avoid detection by the immune system. By binding to TIGIT, domvanalimab is expected to free up immune activating pathways and activate immune cells to attack and kill cancer cells. Domvanalimab is being evaluated in four registrational Phase 3 studies across lung and gastrointestinal cancers, including: (1) ARC-10, evaluating domvanalimab plus zimberelimab versus pembrolizumab in first-line locally advanced or metastatic PD-L1 ≥50% NSCLC; (2) PACIFIC-8, being operationalized by AstraZeneca, evaluating domvanalimab plus durvalumab in unresectable Stage 3 NSCLC; (3) STAR-121, evaluating domvanalimab plus zimberelimab and chemotherapy versus pembrolizumab plus chemotherapy in first-line PD-L1-unselected NSCLC; and (4) STAR-221, evaluating domvanalimab plus zimberelimab and chemotherapy versus nivolumab plus chemotherapy in first-line locally advanced, unresectable or metastatic gastric, esophageal and gastro-esophageal junction adenocarcinomas.

On December 19, 2022 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported that Helen Sabzevari, PhD, President and CEO of Precigen, will present a corporate and clinical overview at the 41st Annual J.P. Morgan Healthcare Conference on Wednesday, January 11, 2023 at 3:45 PM PT/6:45 PM ET in San Francisco, California (Press release, Precigen, DEC 19, 2022, View Source [SID1234625421]).

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Participants may register and view this event through Precigen’s website in the Events & Presentations section at investors.precigen.com/events-presentations.

On December 19, 2022 Mustang Bio, Inc. ("Mustang") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported recent CAR T cell therapy portfolio updates and provided anticipated milestones for 2023 (Press release, Mustang Bio, DEC 19, 2022, View Source [SID1234625420]).

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Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "In 2022, Mustang successfully advanced our CAR T cell therapy portfolio which has laid the foundation for us to achieve multiple milestones in the coming year. Our lead clinical candidate, MB-106, a first-in-class CD20-targeted, autologous CAR T cell therapy for the treatment of relapsed or refractory B-cell non-Hodgkin lymphomas ("B-NHL") and chronic lymphocytic leukemia ("CLL"), continues to progress in our multicenter Phase 1/2 clinical trial. We’re pleased to report that Mustang has met its accrual target for the year for that trial and has manufactured product for all enrolled patients. We look forward to providing first safety and efficacy data in 2023. Additionally, data from the initial ongoing Phase 1/2 clinical trial taking place at Fred Hutchinson Cancer Center ("Fred Hutch") continue to exhibit high efficacy and a favorable safety profile compared to currently approved autologous CAR Ts. In particular, while other cell therapies in development have struggled to show durability of response, we reported in October that twelve of 28 patients enrolled had experienced complete remission (CR) for more than 12 months (10 ongoing), four patients had experienced CR for more than 2 years (all ongoing), and the first patient enrolled was in sustained CR at 33 months."

"In 2023, we anticipate filing an Investigational New Drug application ("IND") for our combination therapy MB-109 to treat glioblastoma ("GBM"). Additionally, we continue to collaborate with the Mayo Clinic to progress our exclusively licensed novel in vivo CAR T technology platform and anticipate the publication of proof-of-concept research in a murine tumor model. We’re looking forward to another productive year across our CAR T therapy programs, as we continue working with our world-class partners to advance therapies for difficult-to-treat cancers and rare diseases," said Dr. Litchman.

CAR T Candidate Portfolio Highlights:

MB-106 (first-in-class CD20-targeted, autologous CAR T cell therapy)
To date, six patients have been enrolled in Mustang’s multicenter Phase 1/2 clinical trial and five patients have been infused at the starting dose levels of their respective protocol arms. Mustang has successfully manufactured product for all enrolled patients at its facility in Worcester, MA. In 2023, the Company anticipates dose escalation and reporting response data at a major medical meeting.

As previously reported, MB-106 continues to demonstrate high efficacy and a favorable safety profile across patients with a wide range of hematologic malignancies in a Phase 1 investigator-sponsored trial at Fred Hutch, including a 100% overall response rate in patients with Waldenstrom macroglobulinemia ("WM"), a rare form of blood cancer. Given this, Mustang plans to treat patients with WM in the Phase 1 portion of its multicenter clinical trial to support a fast-to-market Phase 2 strategy for this indication. Data from the Fred Hutch clinical trial also support the potential of MB-106 to be administered as outpatient therapy and provide a best-in-class immunotherapy option for patients treated previously with CD19-directed CAR T cell therapy. In 2023, Mustang anticipates the U.S. Food and Drug Administration granting Orphan Drug Designation in at least one additional CD20 positive malignancy.

MB-109 (MB-101 (IL-13Rα2 targeted CAR T cell therapy) + MB-108 oncolytic virus)
Preclinical data presented at American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 ("AACR") supported this combination therapy to optimize results to treat recurrent GBM. The combination leverages MB-108 to make cold tumors "hot," thereby improving the efficacy of MB-101 CAR T cell therapy. Data presented separately on MB-101 and MB-108 showed infusions were well tolerated in highly refractory GBM patients. Two patients treated solely with MB-101 who had high levels of intratumoral CD3+ T cells pre-therapy (i.e., "hot" tumors) achieved complete responses lasting 7.5 and 31+ months, respectively. Phase 1 clinical trials of MB-101 at City of Hope and of MB-108 at the University of Alabama at Birmingham continue to enroll patients. Additionally, Mustang will advance the preclinical investigation of MB-109 and plans to file an IND for this treatment in 2023.

MB-102 (CD123-targeted CAR T cell therapy)
The Safety Review Team ("SRT") composed of Investigators and Mustang representatives recently met to assess the progress and safety data from the ongoing Mustang-sponsored, open label, multicenter Phase 1/2 clinical trial to evaluate the safety and efficacy of MB-102 in patients with relapsed or refractory blastic plasmacytoid dendritic cell neoplasm ("BPDCN"), a rare form of leukemia. After thoroughly reviewing the safety data from Dose Level 1 (100 x 106 CAR T cells), the SRT unanimously recommended dose escalation to Dose Level 2 (300 x 106 CAR T cells). There are currently no curative treatments for BPDCN. The trial continues to enroll and study sites include City of Hope, where the CAR T cell therapy was initially developed, Dana-Farber Cancer Institute, Duke University and The University of Texas MD Anderson Cancer Center. The MB-102 clinical trial is the first under Mustang’s IND in which a patient was dosed with cells processed in its own manufacturing facility. In 2023, Mustang expects to provide information about Dose Level 2 after that level is fully enrolled and the SRT has reviewed the data.

In vivo CAR-T platform technology
Mustang executed an exclusive license agreement with Mayo Clinic for this novel technology that may transform the administration of CAR T therapies. The Mayo approach involves activating immune cells in vivo using natural methods employed by the body to deal with infection, thus having the potential to reduce toxicities associated with traditional CAR T therapy. Successful implementation of this technology could lead to an off-the-shelf product with no need to isolate and expand patient T cells ex vivo in a manufacturing facility. Published proof-of-concept data from murine tumor model studies are anticipated in 2023. Additionally, Mustang plans to file an IND application for a multicenter Phase 1 clinical trial once a lead CAR construct has been identified.

On December 19, 2022 Biogen Inc. (Nasdaq: BIIB) reported that it has reached an agreement with Genentech, a member of the Roche Group, related to the commercialization and sharing of economics for glofitamab (Press release, Biogen, DEC 19, 2022, View Source [SID1234625417]). Under the terms of the agreement, Biogen will have no payment obligations and will receive tiered royalties on potential net sales of glofitamab within the United States as part of the companies long-standing collaboration on antibodies targeting CD20.

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Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody being developed by Roche for the treatment of B-cell non-Hodgkin’s lymphomas, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other blood cancers1. Glofitamab is based on a novel structural format called ‘2:1’, which is engineered to have two ‘Fab’ regions that bind to CD20 and one ‘Fab’ region which binds to CD3. This dual targeting activates and redirects a patient’s own T-cells to engage and eliminate cancer B cells.

Data from the Phase II NP30179 study investigating glofitamab in patients with relapsed/refractory (R/R) DLBCL have been submitted for review to the European Medicines Agency (EMA), and submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration, are ongoing. If approved, glofitamab has the potential to be a first-in-class fixed-duration CD20xCD3 T-cell engaging bispecific antibody in DLBCL.

Genentech will have sole decision-making rights on the commercialization of glofitamab within the United States and, in the event of approval, Biogen is eligible to receive tiered royalties in the mid-single digits range on potential net sales of glofitamab within the United States.

Glofitamab, together with mosunetuzumab, is part of the Roche and Genentech CD20xCD3 antibody portfolio that seeks to address the unmet needs of people living with blood cancers. In January 2022, Biogen exercised the option to have joint decision-making rights related to the development and potential commercialization of mosunetuzumab, and Genentech will continue to lead the strategy and implementation of the program. The companies have had a collaboration on antibodies targeting CD20 since 1995.

On December 19, 2022 Atara Biotherapeutics, Inc. (Nasdaq: ATRA) and Pierre Fabre reported that the European Commission (EC) has granted marketing authorization for Ebvallo (tabelecleucel) as a monotherapy for the treatment of adult and pediatric patients two years of age and older with relapsed or refractory Epstein‑Barr virus positive post‑transplant lymphoproliferative disease (EBV+ PTLD) who have received at least one prior therapy (Press release, Atara Biotherapeutics, DEC 19, 2022, View Source [SID1234625415]). For solid organ transplant patients, prior therapy includes chemotherapy unless chemotherapy is inappropriate.

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The approval follows a positive opinion in October by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and is applicable to all 27 European Union member states plus Iceland, Norway, and Liechtenstein. The CHMP positive opinion is based on results from the pivotal Phase 3 ALLELE study.1 In this study, EbvalloTM demonstrated a favorable risk-benefit profile.

"The approval of EbvalloTM in Europe is a medical breakthrough for patients with significant unmet need," said Pascal Touchon, President and Chief Executive Officer of Atara. "As the first allogeneic, or donor-derived, T-cell immunotherapy to receive approval from any regulatory agency in the world, this marks a historic moment for Atara, our European partner, Pierre Fabre, and for the broader cell therapy field."

EBV+ PTLD is a rare, acute, and potentially deadly hematologic malignancy that occurs after transplantation when a patient’s T-cell immune response is compromised by immunosuppression. It can impact patients who have undergone solid organ transplant (SOT) or allogeneic hematopoietic cell transplant (HCT). Poor median survival of 0.7 months and 4.1 months for HCT and SOT, respectively, is reported in EBV+ PTLD patients for whom standard of care failed, underscoring the significant need for new therapeutic options.

Under a previously announced License Agreement with Atara, Pierre Fabre will lead all commercialization and distribution activities in Europe and select other markets, in addition to medical and regulatory activities following the transfer of the EbvalloTM Marketing Authorization Application (MAA) from Atara to Pierre Fabre.

"Ebvallo represents a significant moment in the cell therapy space and a breakthrough for European patients with EBV+ PTLD," said Eric Ducournau, CEO of Pierre Fabre, Atara’s commercialization partner in Europe. "We are proud and excited to bring this innovative therapy to the marketplace, which will reinforce Pierre Fabre’s portfolio in oncology, hematology, and rare diseases."

EbvalloTM has orphan designation in Europe. Orphan designation is reserved for medicines treating life-threatening or chronically debilitating diseases that are rare (affecting not more than five in 10,000 people in the EU). Authorized orphan medicines benefit from ten years of market exclusivity, protecting them from competition with similar medicines with the same therapeutic indication, which cannot be marketed during the exclusivity period.