On September 16, 2024 GV20 Therapeutics, a clinical-stage AI-based next generation biotherapeutics company, reported presentation of clinical results from its Phase 1/2 study of GV20-0251 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain (Press release, GV20 Therapeutics, SEP 16, 2024, View Source [SID1234646674]).

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Dr. Kristopher Wentzel from The Angeles Clinic and Research Institute gave an oral presentation on the clinical data from the monotherapy dose escalation portion of the ongoing study of GV20-0251, a first-in-class antibody targeting the novel immune checkpoint IGSF8, in patients with advanced solid tumors (NCT05669430).

Key highlights from the presentation include:

Patient Population: The study enrolled 38 heavily pre-treated patients across six dose levels and two dosing schedules. The median age was 62 years, with a median of 4 prior lines of treatment.

Safety: GV20-0251 was well-tolerated across all dose levels (0.5 to 20 mg/kg) with no dose-limiting toxicities observed. Most of treatment-related adverse events were grade 1/2, with only one case of grade 3 pneumonitis reported.

Efficacy: Two confirmed partial responses were observed in 12 efficacy-evaluable metastatic cutaneous melanoma patients. Additionally, 14 of 29 efficacy-evaluable patients showed stable disease, including 4 with tumor shrinkage.

Pharmacokinetics: Dose-proportional pharmacokinetics with half-life around 25.6 days and full target occupancy on circulating T cells were observed at doses ≥ 3 mg/kg.
Click here to access the ESMO (Free ESMO Whitepaper) presentation.

"We are excited by these encouraging results for GV20-0251, which represent a significant milestone as the first clinical data for an AI-designed antibody against an AI-predicted target," said Dr. Shirley Liu, Co-founder and Chief Executive Officer of GV20 Therapeutics. "The favorable safety profile and preliminary efficacy signals, particularly in melanoma patients, support the potential of IGSF8 as a novel immune checkpoint target."

GV20-0251 is designed to enhance NK cell killing of malignant cells, upregulate dendritic cell antigen presentation, and increase T cell signaling. This mechanism of action may be particularly relevant for patients with antigen presentation-deficient tumors, which are often resistant to current immune checkpoint inhibitors.

The company is currently recruiting anti-PD1-relapsed and refractory cancer patients to be treated by GV20-0251 in combination with pembrolizumab to further evaluate the drug safety, pharmacokinetics, pharmacodynamics, and efficacy.

On September 16, 2024 Mauna Kea Technologies (Euronext Growth: ALMKT), inventor of Cellvizio, the multidisciplinary probe and needle-based confocal laser endomicroscopy (p/nCLE) platform, reported the publication in the peer-reviewed Journal of Thoracic Disease of new ground-breaking clinical results demonstrating the efficacy of its needle-based Confocal Laser Endomicroscopy (nCLE) technology for the characterization of peripheral lung cancer and preparation of surgical resection (Press release, Mauna Kea Technologies, SEP 16, 2024, View Source [SID1234646690]).

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This study, conducted by the team of Professor Stéphane Renaud at the University Hospital of Nancy, evaluated the use of Cellvizio’s nCLE platform in combination with Electromagnetic Navigation Bronchoscopy (ENB) to characterize suspicious pulmonary nodules and prepare them for surgical resection when needed. The results highlight the potential of nCLE to rapidly and accurately identify malignant lesions while minimizing the risks associated with traditional diagnostic methods including ionizing radiation.

The study included 30 patients with suspicious pulmonary nodules with a median size of 16 mm. The findings revealed a sensitivity of 96.43% and a specificity of 100% in characterizing malignant lesions, based on previously published nCLE image classification. The median time of contact with the suspicious lesions was just 5 minutes with no major complications reported, demonstrating the technology’s efficiency in clinical practice. Additionally, the use of nCLE also improved the quality and quantity of tissue sampling, thus enabling molecular and genomics analyses, which have become essential tools for the choice and planning of treatments.

Professor Stéphane Renaud, Thoracic Surgeon at University Hospital Nancy and principal investigator of the study, stated: "We are extremely pleased with the results of this study, which brings to light the high diagnostic value of needle-based endomicroscopy in combination with Electromagnetic Navigation Bronchoscopy and its ability to improve our treatment planning and minimize patient risk. With a much-enhanced ability to target our biopsies, we have also been able to obtain essential tissue material for molecular and genomics analyses, which are crucial for guiding immunotherapy strategies. This combination of technologies will certainly play a key role in the fight against lung cancer in the future."

"We are thrilled by these outstanding clinical results, which reinforce the value of our needle-based endomicroscopy platform in advancing the field of lung cancer diagnostics and treatment," commented Sacha Loiseau, Ph.D., Chairman and CEO of Mauna Kea Technologies. "This study confirms that Cellvizio can play a pivotal role not only in enabling real-time, accurate, and minimally invasive diagnosis, but also in helping physicians improve their treatment planning and, in turn, patient outcomes."

On September 16, 2024 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported new ADG126 clinical data presented at the ESMO (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain, September 13-17 (Press release, Adagene, SEP 16, 2024, View Source [SID1234646641]).

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The poster, titled Increased Therapeutic Index of Muzastotug (ADG126), a Masked Anti-CTLA-4 Antibody, in Combination with Pembrolizumab (Pembro) Enables Significant Clinical Benefits and Supports Further Clinical Development in Patients with Metastatic MSS CRC, reports data from an ongoing phase 1b/2 trial of Adagene’s masked anti-CTLA-4 SAFEbody in combination with Merck & Co., Inc., Rahway, NJ, USA’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) (ADG126-P001; NCT05405595).

"I am delighted that the ESMO (Free ESMO Whitepaper) data show a promising overall response rate, progression-free survival (PFS) and early survival benefit from treatment with the immunotherapy (IO) doublet of ADG126 in combination with pembrolizumab for patients with advanced/metastatic MSS CRC, the largest segment of colorectal cancer with few treatment options," said Daneng Li, MD, Associate Professor in the Department of Medical Oncology & Therapeutics Research at the City of Hope Comprehensive Cancer Center, and a study investigator. "With a much higher dosing level than available anti-CTLA-4 therapies, these data reinforce the encouraging safety and efficacy profile for ADG126 administered repeatedly in MSS CRC."

Dr. Li continued, "Given the best-in-class potential for ADG126, this combination with pembrolizumab could address even broader patient populations, such as those with liver metastases, particularly if combined with standard of care to control early disease progression. Further, the safety profile of this immunotherapy doublet enables repeat cycles to achieve and sustain sufficient drug exposure that maximizes potential for a long-term survival benefit."

ADG126 is a masked anti-CTLA-4 SAFEbody targeting a unique epitope of CTLA-4 on regulatory T cells (Tregs) in tumor tissue which shows potential best-in-class safety and efficacy profiles in combination with pembrolizumab. The unique epitope of ADG126 alone has shown enhanced antibody-dependent cell mediated cytotoxicity without Fc engineering, which is associated with significantly increased toxicity. Further, it has shown minimal immunogenicity and anti-drug antibodies, with no impact on its pharmacokinetic (PK) profile.

Key highlights from the poster (July 30, 2024 data cutoff) include:

· ADG126 in combination with pembrolizumab continued to demonstrate a differentiated safety profile in dose escalation and dose expansion cohorts for heavily pre-treated advanced/metastatic patients with solid tumors (n=66):

o No dose-limiting toxicities (DLT) or Grade 4 or 5 TRAEs were observed at any dose up to 20 mg/kg Q3W, which was evaluated in dose escalation (n=6) to support an ongoing loading dose cohort.

o No Grade 3 colitis was observed at any dose, with limited use of infliximab to manage immune-mediated diarrhea/colitis in no more than 10% of patients.

o No significant late-onset toxicities were observed after repeat dosing at the 10 mg/kg dose level. TRAEs by week from treatment start are summarized in the poster.

o Grade 3 TRAEs occurred in only 6% of patients at the 10 mg/kg Q6W dose (1/17) and 16% of patients at the 10 mg/kg Q3W dose (6/37). Standard of care treatments are associated with higher rates of toxicities.

o Seven patients developed treatment related SAEs; however, the discontinuation rate remains low at 8% (5/66).

· ADG126 administered at 10 mg/kg Q6W or Q3W in combination with pembrolizumab (200 mg/Q3W) demonstrated an encouraging efficacy signal, durable disease control and an early survival benefit in MSS CRC patients, with dose-dependent efficacy and objective responses per RECIST criteria observed for the Q3W schedule:

o In the subset of efficacy evaluable patients without liver and peritoneal metastases (n=17) who received ADG126 10 mg/kg Q3W, an ORR of 24% was observed, including four confirmed PRs. These results are consistent with earlier ORR data published at ASCO (Free ASCO Whitepaper) GI 2024. Response rates for current standard of care treatments range from 1% to 6.3%*.

o An additional 11 patients had stable disease (SD) for an overall disease control rate (DCR) of 88% (15/17).

o Further, a median PFS of 8.5 months was observed in the subset at the ADG126 10 mg/kg Q3W dose and median PFS was 5.9 months for patients at the ADG126 10 mg/kg Q6W dose.

o The 12-month OS rates were 74% for those patients without liver metastases (n=36), and 82% in those without liver and peritoneal metastases (n=24) in the combined 10 mg/kg Q6W and Q3W cohorts.

o While the 10 mg/kg Q3W cohort demonstrated efficacy with RECIST responses and the Q6W did not, early OS rates appear comparable for both doses. This suggests that the Q6W could be used as a starting point for future combination trials, or as a dose modification strategy for safety management.

o Additionally, results in patients without liver metastases who received at least four cycles of the combination showed comparable OS rates to those without liver and peritoneal metastases, highlighting the importance of early disease control with standard of care to enable the IO doublet to drive a long-term survival benefit.

· In dose escalation, the 20 mg/kg Q3W dose level was tolerable for the initial cycle (n=6). Based upon the safety profile of the initial dose, 20 mg/kg is being evaluated as a loading dose in an expansion cohort that has enrolled 12 patients. This cohort is evaluating a single dose of ADG126 at 20 mg/kg followed by a 10 mg/kg Q3W maintenance dose in combination with pembrolizumab. Initial data for this cohort are expected later this year.

· Comprehensive PK and exposure response analyses were also conducted to provide insight on various dosing regimens and their correlation to safety and efficacy of the combination. These results reinforce the increased therapeutic index of ADG126, underscoring a key advantage of the SAFEbody precision masking technology. The extensive PK data also guide future clinical development and dose selection to meet FDA’s Project Optimus dose optimization requirements.

Commenting on these promising results, Peter Luo, Adagene’s CEO and President of R&D said, "We are thrilled that today’s update continues to reinforce the clinical benefits of the best-in-class therapeutic potential for ADG126 at the 10 mg/kg dose level in combination with pembrolizumab in MSS CRC. Armed with these results and the anticipated findings from our ongoing 20 mg/kg loading dose regimen, we are moving ahead with plans to evaluate ADG126 in MSS CRC at 10- to 20-fold higher doses than ipilimumab in a randomized, registration-oriented clinical program. With safety comparable to historical data for pembrolizumab monotherapy, these data provide a solid foundation for the potential of an IO doublet targeting CTLA-4 and PD-1 to move into earlier lines of therapy and broader patient populations, particularly when combined with standard of care aiming for a transformational improvement in patient outcomes."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

SAFEbody is a registered trademark in the United States, China, Australia, Japan, Singapore, and the European Union.

On September 17, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported updated efficacy and safety results from the TAMARACK Phase 2 study of vobramitamab duocarmazine (vobra duo), an antibody-drug conjugate (ADC) that targets B7-H3, for patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, MacroGenics, SEP 16, 2024, View Source [SID1234646659]). The data were featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain from September 13-17, 2024.

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"A key reason for conducting the TAMARACK study was to test the hypothesis that we could improve upon the duration of vobra duo treatment observed in the Phase 1 study by reducing the starting dose from 3.0 mg/kg to either 2.0 or 2.7 mg/kg and increasing the dosing interval from every three weeks to every four weeks. In doing so, our aim was to improve safety and tolerability, extend the treatment duration and achieve improved rPFS as compared to the result in our Phase 1 mCRPC dose expansion cohort," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We believe that these latest results from TAMARACK continue to demonstrate that vobra duo is an active drug in prostate cancer. Ultimately, our path forward for the molecule will depend on the final safety and efficacy data, including mature median rPFS, which we expect to have in hand no later than early 2025. We expect to make decisions about potential future development in the context of a competitive treatment landscape assessment, resource allocation across our clinical portfolio and potential partnering opportunities for vobra duo."

TAMARACK Study Demographics

The abstract submitted to ESMO (Free ESMO Whitepaper) was based on a data cut-off as of April 12, 2024; updated data based on a cut-off date of July 9, 2024, are included below and are reported in the Company’s poster presentation at ESMO (Free ESMO Whitepaper).
The TAMARACK trial enrolled a total of 181 participants, with 176 participants receiving at least one dose of vobra duo at either 2.0 mg/kg q4W (n=90) or 2.7 mg/kg q4W (n=86). As of the data cut-off date, 23 and 16 participants remained on treatment in the 2.0 mg/kg and 2.7 mg/kg cohorts, respectively. While mCRPC study participants are no longer being dosed in the study, participants continue to be monitored for adverse events, disease progression, and survival.
Baseline Characteristics:
•Enrolled study participants had a median age of 70 years (range, 35-89).
•88 Study participants (48.6%) had an ECOG performance status of 1 or 2.
•30 Study participants (16.6%) had visceral disease at baseline, with liver or lung disease in 25 participants (13.8%).
•81 Study participants (44.8%) had measurable disease at baseline, and 97 (53.6%) had received prior taxane.
•Both treatment arms were well-balanced across most baseline characteristics, including prior use of taxanes, androgen receptor axis-targeted (ARAT) treatment, poly-ADP ribose polymerase (PARP) treatment, and baseline PSA.
TAMARACK Efficacy Results as of July 9, 2024 Cut-off Date
Overall, the Company believes that the results to date from the TAMARACK study indicate antitumor activity associated with vobra duo in mCRPC as demonstrated by the protocol-specified primary endpoint of landmark 6-month radiographic progression-free survival (rPFS) rate, as well as other measures of tumor response.
•In the intent-to-treat (ITT) population, 6-month rPFS rate was 69% for the 2.0 mg/kg arm (95% CI, 57-79) and 70% for the 2.7 mg/kg arm (95% CI, 58-79).
•Landmark 6-month rPFS rates were consistent across taxane-naïve study participants (ranging from 66-82%) and taxane pre-treated study participants (ranging from 60-73%), regardless of treatment arm.

•Although immature, with only 65 PFS events (35.9%) as of the data cut-off, median rPFS was approximately 8.5 months for the 2.0 mg/kg cohort (95% CI, 7.2-11.2) and 7.5 months for the 2.7 mg/kg cohort (95% CI, 7.2-10.6). Because these results were immature as of the cutoff date, they are likely to change as additional events accrue.
Tumor response rates
•Out of 45 RECIST-response evaluable patients in the 2.0 mg/kg arm, the confirmed objective response rate (ORR) was 20.0% (n=9) and the unconfirmed ORR was 26.7% (n=12).
•Out of 32 RECIST-response evaluable patients in the 2.7 mg/kg arm, the confirmed ORR was 40.6% (n=13) and the unconfirmed ORR was 46.9% (n=15).
•Confirmed ORR was comparable between taxane-naïve study participants (26.7%, n=12/45) and taxane pre-treated study participants (17.5%, n=11/63), regardless of treatment arm.
•Tumor responses did not appear to correlate with baseline B7-H3 expression based on archival tissue samples of mixed age.
TAMARACK Safety Results as of July 9, 2024 Cut-off Date
Overall summary of adverse events (AEs)
•In the 2.0 mg/kg cohort, 65.6% of study participants (n=59) experienced a Grade ≥3 treatment-emergent AE (TEAE); this cohort had a discontinuation rate of 25.6% (n=23) and a dose reduction rate of 50.0% (n=45) due to TEAEs.
•In the 2.7 mg/kg cohort, 62.8% of study participants (n=54) experienced a Grade ≥3 TEAE; this cohort had a discontinuation rate of 38.4% (n=33) and a dose reduction rate of 54.7% (n=47) due to TEAEs.
•The most common (occurring in ≥20% of study participants) all-grade TEAEs were: asthenia, edema peripheral, decreased appetite, nausea, pleural effusion, diarrhea, fatigue, constipation, anemia, palmar-plantar erythrodysesthesia (PPE, or hand-foot syndrome), neutropenia, and stomatitis. The majority of TEAEs with a ≥10% incidence rate in either treatment arm was limited to Grade 1/2 events.
•Rates of pleural effusion, pericardial effusion, and PPE for both the 2.0 mg/kg cohort (28.8%, 13.3%, 18.9%, respectively) and the 2.7 mg/kg cohort (44.2%, 17.5%, 28%, respectively) decreased compared to the Phase 1 mCRPC dose expansion cohort (48.8%, 17.1%, 46.3%, respectively), despite an increased median number of doses of vobra duo administered on TAMARACK.

•Eight fatal treatment-related AEs as assessed by the treating physician: five in the 2.0 mg/kg cohort and three in the 2.7mg/kg cohort. These include three events of pneumonitis, and one event each of cardiac failure, stress cardiomyopathy, ventricular fibrillation, pleural effusion, and gastrointestinal hemorrhage.
•Rates of treatment-related AEs (including all grades and Grade ≥3) and treatment-related severe AEs were similar between taxane-naïve and taxane pre-treated study participants.

Tolerability findings

•In the 2.0 mg/kg cohort, 25.6% of study participants (n=23) remained on study drug as of July 9, 2024. Study participants received a median number of 6 doses (range, 1-11), with a median dose intensity (calculated as a percentage of the total planned dose that was administered) of 92.6% (range, 64.2-106.1%).
•In the 2.7 mg/kg cohort, 18.6% of study participants (n=16) remained on study drug as of the data cut-off date. Study participants received a median number of 6 doses (range, 1-12), with a median dose intensity of 81.7% (range, 40.5-104.3%).
•Taxane-naïve study participants experienced higher rates of dose reductions due to TEAEs (62.7%) and dose interruptions due to TEAEs (70.7%) compared to taxane pre-treated study participants (44.6% and 43.6%, respectively).

ESMO Poster Presentation

Title: TAMARACK: Randomized Phase 2 trial of the B7-H3 targeting antibody drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) in metastatic castration-resistant prostate cancer (mCRPC)
Presenter / Lead Author: Johann de Bono, M.D., M.Sc., Ph.D., FRCP, FMedSci, Division of Clinical Studies, Royal Marsden Hospital Institute of Cancer Research, Sutton, UK
Presentation ID: 1654P
Session Date: Sunday, September 15, 2024
Poster Display Time: 9:00 a.m. – 5:00 p.m. CEST
The poster presentation is available for download under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source

Conference Call

The Company will host a conference call to discuss the TAMARACK poster data and provide a general corporate update on Monday, September 16, 2024, at 8:00am ET. The call will be led by Scott Koenig, M.D., Ph.D., President and Chief Executive Officer; Stephen Eck, M.D., Ph.D., Senior Vice President – Chief Medical Officer; and Jim Karrels, Senior Vice President – Chief Financial Officer.

To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source A recorded replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

About Vobra Duo and the TAMARACK Study

Vobra duo is an antibody-drug conjugate (ADC) that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation. The TAMARACK Phase 2 study of vobra duo is being conducted in participants with mCRPC who were previously treated with one prior androgen receptor axis-targeted therapy (ARAT). Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. The TAMARACK study is designed to evaluate vobra duo at two different doses: 2.0 mg/kg or 2.7 mg/kg every four weeks (q4W).

On September 16, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported updated data, including median progression-free survival (mPFS) and overall survival (OS) findings, from the Phase 2 trial of zanidatamab, an investigational dual HER2-targeted bispecific antibody, in combination with chemotherapy as first-line treatment for patients with HER2-expressing advanced or metastatic gastroesophageal adenocarcinoma (mGEA) (Press release, Jazz Pharmaceuticals, SEP 16, 2024, View Source [SID1234646675]).

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Data from 41 patients with HER2-positive mGEA who were treated with zanidatamab in combination with physician’s choice of chemotherapy treatment demonstrated a mPFS of 15.2 [95% CI: 9.5, 33.4] months. After a median duration of follow-up of 41.5 (range, 23.0-52.7) months, the median OS was not mature, a Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0, 78.0] and the 30-month overall survival was 59% [95% CI: 41.0, 73.0].

"Gastroesophageal adenocarcinoma (GEA) represents one of the most common tumor types worldwide; however, developing effective treatment options for GEA patients has been challenging," said Dr. Elena Elimova, lead trial investigator and a medical oncologist at Princess Margaret Cancer Centre, Toronto, Canada. "Despite recent advancements for patients, the sustained clinical antitumor activity seen in this trial demonstrates the potential for zanidatamab to address a significant unmet patient need in HER2-positive GEA."

"The updated results from this Phase 2 trial reaffirm zanidatamab’s potential as a foundational treatment for patients with HER2-positive mGEA and showcase the promise of this HER2-targeted bispecific antibody to treat HER2-expressing cancers," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "We look forward to continuing to advance our broader clinical development program for zanidatamab in GEA, including the Phase 3 first-line clinical trial HERIZON-GEA-01 that is expected to read out in the second quarter of 2025, and other HER2-expressing solid tumors, with the goal of supporting more patients with HER2-positive cancers."

Phase 2 mGEA Trial Results
The data include efficacy and tolerability findings from an ongoing, open-label Phase 2 study (NCT03929666) evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with HER2-expressing mGEA, which comprises gastric, esophageal and gastroesophageal junction (GEJ) adenocarcinomas. Patients had not received prior HER2-targeted agents nor systemic treatment for mGEA. A total of 46 patients with HER2-expressing mGEA (41 patients with HER2-positive mGEA) were enrolled from 15 sites across the United States, Canada and South Korea, and patients were administered zanidatamab with physician’s choice of chemotherapy treatment. Currently, chemotherapy-based regimens are the standard first-line combination therapy for 1L mGEA.

The longer-term data (median duration of follow-up of 41.5 [range, 23.0-52.7] months) demonstrates the promising antitumor activity of zanidamatab combined with chemotherapy as a first-line therapy for HER2-positive mGEA.

Treatment with zanidatamab resulted in a cORR of 84% [95% CI: 68.0, 94.0], an increase of 5% from the cORR previously reported, and one additional patient achieved a complete response for a total of four patients achieving complete response among 37-response evaluable patients.
The median duration of response was 18.7 months [95% CI: 8.3-NE] with 10 patients having an ongoing response at the time of data cutoff.
The mPFS was 15.2 [95% CI: 9.5, 33.4] months.
The Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0, 78.0] with a 30-month overall survival of 59% [95% CI: 41.0, 73.0].
With additional follow-up, the safety and tolerability profile of zanidatamab plus chemotherapy remained manageable with no new safety signals identified. Diarrhea was the most common Grade 3-4 treatment-related adverse events (TRAEs) (35%); the incidence of Grade 3-4 diarrhea was <15% for patients treated after the implementation of mandated antidiarrheal prophylaxis. Treatment discontinuation due to TRAEs were infrequent, and there were no treatment-related deaths.

These data were presented in a poster session entitled Zanidatamab + Chemotherapy for First-Line Treatment for HER2+ Advanced or Metastatic Gastroesophageal Adenocarcinoma (mGEA) during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting taking place in Barcelona, Spain. The presentation is available to conference registrants on the ESMO (Free ESMO Whitepaper) conference website (Presentation Number 1423P).

Jazz continues to enroll patients in the Phase 3 randomized clinical trial, HERIZON-GEA-01 (NCT05152147), evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing mGEA. This is an events-based trial; top-line data from this trial is expected to read out in the second quarter of 2025.

Phase 2 Colorectal Cancer (CRC) Trial Results Presented as Mini-Oral at ESMO (Free ESMO Whitepaper) 2024
In addition to the mGEA trial presentation, a mini-oral was also presented at ESMO (Free ESMO Whitepaper) 2024 from another arm of the same Phase 2, open-label trial (NCT03929666) that includes a cohort of patients with metastatic CRC treated with first-line zanidatamab plus chemotherapy ± bevacizumab (bev). In 11 response-evaluable patients, there were 10 confirmed partial responses and 1 patient with stable disease as a best response. The cORR was 91% (95% CI: 58.7, 99.8) and median duration of response was not reached (2.9+,16.7+ months). All patients experienced TRAEs – Grade 3-4 TRAEs occurred in five (38%) patients, three (23%) of whom experienced diarrhea. No patients discontinued zanidatamab due to a TRAE and there were no treatment-related deaths. Zanidatamab plus chemotherapy ± bev demonstrated encouraging antitumor activity with a generally manageable safety profile as first-line treatment for patients with HER2-positive mCRC.

About Zanidatamab
Zanidatamab is an investigational dual HER2-targeted bispecific antibody that simultaneously binds to two distinct sites on HER2, known as biparatopic binding. This unique design and enhanced binding results in multiple mechanisms of action, including HER2 and HER3 signal blockade, removal of HER2 protein from the cell surface and enhanced immune effector functions, such as complement-dependent cytotoxicity (CDC), which leads to encouraging antitumor activity. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review of the Biologics License Application (BLA) for zanidatamab with a Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024. Zanidatamab was also granted Breakthrough Therapy designation in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC) and given two Fast Track designations: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

About Gastroesophageal Adenocarcinoma
Gastroesophageal adenocarcinoma (GEA) is the fifth most common cancer worldwide, and approximately 20% of patients have HER2–positive disease.1,2,3 HER2–positive GEA has high morbidity and mortality, and patients are urgently in need of new treatment options.