On December 19, 2022 Zymeworks Inc. (NASDAQ: ZYME), a clinical-stage biotechnology company developing multifunctional biotherapeutics, reported positive topline results from the pivotal Phase 2b HERIZON-BTC-01 open-label, single-arm clinical trial investigating zanidatamab, a HER2-targeted bispecific antibody, as monotherapy in patients with previously treated HER2-amplified and expressing BTC (Press release, Zymeworks, DEC 19, 2022, View Source [SID1234625426]).

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The positive topline results showed that 41.3% (95% CI: 30.4, 52.8) of enrolled patients with HER2-amplified and expressing (IHC2+ and 3+) disease achieved an objective response as assessed by independent central review. The median duration of response was 12.9 months (95% CI: 5.95 to not reached). The safety profile of zanidatamab in this trial was consistent with that observed in previously reported monotherapy studies, with no new safety signals identified. Full results from the pivotal trial are expected to be presented at a medical meeting in 2023.

Biliary tract cancers, including gallbladder cancer and cholangiocarcinoma, are diagnosed in more than 210,000 people every year1, with most patients presenting with inoperable disease2. Disease control with front-line therapy is modest and patients need treatment options after progression3,4. The human epidermal growth factor receptor 2 (HER2) is a promising target in approximately 5%-10% of cholangiocarcinomas and up to 20% of gallbladder cancers5. Currently no HER2-targeted therapy has been approved for the treatment of BTC.

"Through our work with the BTC patient community, we see first-hand the challenge these patients face in not only getting a diagnosis, but in the limited treatment options available," said Stacie Lindsey, Founder & CEO of the Cholangiocarcinoma Foundation. "Each investigative trial begins to close the gap on this high unmet medical need by helping to bring more treatment options to BTC patients and we’re looking forward to watching zanidatamab’s progression through the global regulatory review process."

"We are thrilled to report these positive topline data from the HERIZON-BTC-01 clinical trial, which further support the potential of zanidatamab as a new chemotherapy-free therapeutic option for HER2-amplified and expressing BTC. These data demonstrate that zanidatamab, as a single agent, improves on the current standard of care for patients in a difficult-to-treat disease who currently have a poor prognosis based on the limited treatment options currently available," said Neil Josephson, M.D., Chief Medical Officer at Zymeworks. "I want to thank all of the patients, their families and the investigators who participated in this important study."

Conference Call for Investors and Analysts

Zymeworks management will host a conference call and webcast for investors and analysts on December 19, 2022 at 8:00 am ET. The event will be webcast live with dial-in details and webcast replays available on Zymeworks’ website at View Source

About HERIZON-BTC-01

HERIZON-BTC-01 is a global, multicenter, open-label, single-arm study (NCT04466891) with a primary endpoint of confirmed objective response rate (cORR) by independent central review (ICR) per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary endpoints include duration of response (DOR), proportion of subjects with a DOR ≥16 weeks, disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. HER2 amplification, as determined centrally by in situ hybridization (ISH) in tumor tissue, was an inclusion criterion for all subjects enrolled into the two study cohorts: Cohort 1, the primary efficacy cohort, with tumor tissue showing HER2 immunohistochemistry (IHC) 2+ or 3+ staining, and Cohort 2 with tumor tissue showing HER2 IHC 0 or 1+ staining. The study was initiated in July 2020 and has active sites in North America, Asia Pacific, Europe, and South America, and shares sites with the pivotal Phase 3 trial, HERIZON-GEA-01 (NCT05152147), in first-line gastroesophageal adenocarcinoma (GEA) patients.

About Zanidatamab

Zanidatamab is an investigational, bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2, and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks continues to enroll subjects in the Phase 3 randomized clinical trial, HERIZON-GEA-01, evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab for HER2-expressing GEA. Zymeworks has entered into separate agreements with each of BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each of BeiGene and Jazz with exclusive rights to develop and commercialize zanidatamab throughout various countries around the world.

Zymeworks has an ongoing Expanded Access Program (EAP) for use of zanidatamab in patients with HER2-positive advanced solid tumors who are not eligible for zanidatamab clinical trials, meet the criteria for EAP, and who in the opinion of the treating oncologist, would potentially benefit from treatment with zanidatamab. Additional information is available on our website at View Source

On December 19, 2022 Illumina, Inc. (NASDAQ: ILMN) reported that its executives will be speaking at the following investor conference (Press release, Illumina, DEC 19, 2022, View Source [SID1234625424]):

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41st Annual J.P. Morgan Healthcare Conference on January 9, 2023
Presentation at 3:45pm Pacific Time (6:45pm Eastern Time) immediately followed by a Q&A Session to begin at approximately 4:05pm Pacific Time (7:05pm Eastern Time)

The webcast can be accessed through the Investor Info section of Illumina’s website at investor.illumina.com. A replay will be posted on Illumina’s website after the event and will be available for at least 30 days following.

On December 19, 2022 GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, reported that it has entered into a clinical trial collaboration and supply agreement with Merck to start a clinical study of the combination therapy of GFH925 with ERBITUX (cetuximab) as a potential frontline treatment among NSCLC patients harboring KRAS G12C mutation in a multi-center Phase Ib/II trial in Europe (Press release, GenFleet Therapeutics, DEC 19, 2022, View Source [SID1234625423]).

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Preliminary data from phase I clinical study (NCT05005234) of GFH925 monotherapy for the treatment of solid tumors were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting; and a favorable safety/tolerability and promising antitumor activity profile was observed in previously treated advanced NSCLC patients with KRAS G12C mutation.

"We are delighted to reach an agreement with Merck in our mutual efforts to move forward the clinical investigation of GFH925/Erbitux combination therapy in a frontline setting for NSCLC, as the GFH925 monotherapy program is making significant progress in China. We appreciate Merck’s recognition of our fully integrated capabilities in developing innovative products. We are excited for the opportunity to further evaluate the safety/tolerability, as well as efficacy of this promising combination therapy." said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet.

"This trial collaboration will mark the starting point of GenFleet’s multi-regional clinical development in Europe. As we reach an increasing number of milestones in our globalization efforts, we believe our cooperation with Merck will strengthen GenFleet’s competitive advantage with differentiated development strategy and efficiency. Through internal discovery and co-development initiatives, we hope to bring more innovative therapies to patients worldwide." said Jiong Lan, Ph.D., Chief Executive Officer of GenFleet.

Under the terms of the agreement, GenFleet will conduct an open-label study of the combination therapy in previously untreated advanced NSCLC patients. Merck will provide clinical drug supplies of cetuximab in this multi-center trial in Europe. The use of cetuximab as a monotherapy or as a combination therapy has not been approved in any country for patients with advanced NSCLC.

About KRAS & GFH925

RAS protein family can be divided into KRAS, HRAS and NRAS categories. KRAS mutation are detected in nearly 90% of pancreatic cancer, 30-40% of colon cancer, and 15-20% lung cancer patients. The occurrence of KRAS G12C mutation subset is more frequently observed than those with ALK, ROS1, RET and TRK 1/2/3 mutations combined.

By covalently and irreversibly modifying the cysteine residue of KRAS G12C protein, GFH925 inhibits the GTP/GDP exchange, an essential step in pathway activation. Preclinical cysteine selectivity studies demonstrated high selectivity of GFH925 towards G12C. Subsequently, GFH925 inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest.

About ERBITUX (cetuximab)

ERBITUX is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of ERBITUX is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. Based on in vitro evidence, ERBITUX also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).

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.