Category: 3. Business

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Cody Luongo, a media consultant in Charleston, South Carolina, recently became a full-time freelancer after losing his job. In this new phase of his professional life, Luongo told Business Insider that AI has become his “constant companion,” helping him do everything from drafting press releases to refining client pitches.

“AI accelerates my work enough that I can do exponentially more for my clients with their allotted budgets,” he said.

Luongo is far from the only freelancer using AI technology to leverage their skills and services. While integrating AI can be a smart and lucrative choice on an individual level, its impacts on the wider gig economy are decidedly more mixed.

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A 2023 study by Washington University found that AI tools actually caused a decline in the amount of freelance work available and how much companies were willing to pay for that work. The study found that after ChatGPT’s release in 2022 the number of writing-related freelance jobs declined by 2% and monthly earnings declined by 5.2.%. For image-related workers, the drops were even sharper– AI tools led to a 3.7% decline in jobs and a 9.4% decrease in monthly earnings.

“AI definitely lowers the barrier to entry, so it makes many activities accessible for more people,” Washington University assistant marketing professor Xiang Hui, who worked on the study, told BI. While that may sound like a positive thing, especially for those looking to break into the gig economy, Hui’s research shows it’s actually not.

Even the most experienced freelancers aren’t safe from AI’s influence, Hui says.

“The drop in earnings, if anything, is actually larger for high-quality freelancers in comparison with low-quality freelancers,” he told BI. “High quality doesn’t really protect freelancers.”

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Hui attributes this to the fact that less experienced freelancers are able to punch up with AI. These new freelancers use the technology to refine their output until it’s “good enough,” and then push out passable work at a lower price point. While there’s still a clear difference between this “good enough” work and truly excellent work, the difference is negligible, and more experienced gig workers lose their competitive edge.

There are also worries that AI is stifling genuine creativity, something freelancers are often relied on to provide in a world of homogenized output.

“AI can raise the baseline of creativity, but fewer people are having breakthroughs. You need breakthroughs for innovation,” Shane Schweitzer, assistant professor of management and organizational development at Northeastern University’s D’Amore-McKim School of Business, told BI.

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Erin Hatton, a sociology professor at the State University of New York at Buffalo, agrees. “[AI is] being adopted so broadly that it’s, at least eventually, going to prevent people from getting and using key skills,” she told BI.

Overall, experts who spoke to BI agree that AI is beneficial in that it’s lifted the baseline standard of gig work, increasing overall quality. However, they also note that AI has made it much less likely for gig workers to produce something of truly outstanding quality.

In short, AI is raising the floor and lowering the ceiling. “[AI is] not leveling the playing field necessarily,” Schweitzer says. “It’s just creating slightly more competence.”

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This article ‘AI Definitely Lowers The Barrier For Entry,’ Gig Economy Workers Wrestle With How To Proceed As The Technology Infiltrates Their Industries originally appeared on Benzinga.com

The US main transportation safety regulator said on Friday it is seeking information from Tesla about a new driver assistance mode dubbed “Mad Max” that operates at higher speeds than other versions.

Some drivers on social media report that Tesla vehicles using the more aggressive version of its full self-driving (FSD) system could operate above posted speed limits.

“NHTSA is in contact with the manufacturer to gather additional information,” the National Highway Traffic Safety Administration (NHTSA) said in a statement. “The human behind the wheel is fully responsible for driving the vehicle and complying with all traffic safety laws.”

NHTSA earlier this month opened an investigation into 2.9m Tesla vehicles equipped with its full self-driving system due to the dozens of reports of traffic-safety violations and crashes.

NHTSA said in opening the investigation it is reviewing 58 reports of issues involving traffic safety violations when using FSD, including 14 crashes and 23 injuries.

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Tesla did not immediately respond to a request for comment, but last week reposted a social media post that described Mad Max mode as accelerating and weaving “through traffic at an incredible pace, all while still being super smooth. It drives your car like a sports car. If you are running late, this is the mode for you.”

NHTSA said earlier this month that FSD – an assistance system that requires drivers to pay attention and intervene if needed – has “induced vehicle behavior that violated traffic safety laws”.

The agency said it has six reports in which a Tesla vehicle, operating with full self-driving engaged, “approached an intersection with a red traffic signal, continued to travel into the intersection against the red light and was subsequently involved in a crash with other motor vehicles”.

Tesla says FSD “will drive you almost anywhere with your active supervision, requiring minimal intervention” but does not make the car self-driving.

Tesla’s full self-driving, which is more advanced than its autopilot system, has been under investigation by NHTSA for a year. In October 2024, NHTSA opened an investigation into 2.4m Tesla vehicles with FSD after four collisions in conditions of reduced roadway visibility. The Washington Post had previously reported the agency’s interest in the Mad Max mode.

October in much of the U.S. brings cooler weather, vibrant fall colors and, of course, pumpkin-spiced everything. This is peak pumpkin season, with most of the American pumpkin crop harvested in October.

With the pumpkin spice craze fully underway, I find myself thinking more about pumpkins. As an extension specialist working at Oklahoma State University’s botanic garden, I educate the people pouring in to buy pumpkins at our annual sale about the plant’s storied history and its prominence today.

While people often picture pumpkins as bright orange, they actually come in a wide range of colors, including red, yellow, white, blue and even green. They vary in size and texture too: Some are smooth, others warty. They can even be miniature or giant.

The word “pumpkin” comes from the Greek word “peopon,” meaning “large melon.” Botanically, pumpkins are fruits because they contain seeds, and they belong to the squash family, Cucurbitaceae. This family also includes cucumbers, zucchini and gourds. Pumpkins are grown for many purposes: food, seasonal decorating, carving for Halloween and even giant pumpkin contests.

All 50 states produce some pumpkins, with Illinois harvesting the most. In 2023, Illinois grew 15,400 acres of pumpkins. The next largest amount was grown in Indiana, with about 6,500 acres.

Pumpkin yields vary each year, depending on the varieties grown and the growing conditions in each area. The top six pumpkin-producing states are California, Illinois, Indiana, Michigan, Pennsylvania and Washington.

Early pumpkin history

Pumpkins originated in Central and South America, ending up in North America as Native Americans migrated north and carried the seeds with them. The oldest pumpkin seeds discovered were found in Mexico and date back about 9,000 years.

Pumpkins were grown as a crop even before corn or beans, the other two sisters in a traditional Native American “three sisters” garden. The three sister crops – corn, beans and squash – are planted together, and each has a role in helping the others grow.

Native Americans planted corn in the spring, and once the plants were a few inches tall, they planted beans. The beans vine around the corn as it grows, giving them a natural trellis. Beans also have the ability to take nitrogen from the atmosphere, and with the help of bacteria they convert it into forms that plants can use, such as ammonia, for fertilizer.

After the beans started growing, it was time to plant squash, such as pumpkin. Squash leaves covered the ground, shading the soil and helping keep it moist. The giant leaves also helped reduce the number of weeds that would compete with the corn, bean and squash growth.

Every part of the pumpkin plant is edible, even the flowers. Some Native American groups would dry pumpkins’ tough outer shells, cut them into strips and weave them into mats.

Pumpkins were introduced to Europe from North America through the Columbian Exchange. Europeans found that the pumpkins grown in the New World were easier to grow and sweeter than the ones in 1600s England or France, likely due to the weather and soil conditions in the Americas.

Baking American pumpkins

Native Americans introduced early settlers to pumpkins, and the colonists eagerly incorporated them into their diet, even making pies with them.

Early settlers’ pumpkin pies were hollowed-out pumpkins filled with milk, honey and spices, cooked over an open fire or in hot ashes. Others followed English traditions, combining pumpkin and apple with sugar and spices between two crusts.

The custard-style pumpkin pie we know today first appeared in 1796 as part of the first cookbook written and published in the United States, “American Cookery,” by Amelia Simmons. There were actually two pumpkin pie recipes: one used mace, nutmeg and ginger, the other just allspice and ginger.

The pumpkin spice craze

Pumpkin spice as one mixed ingredient was sold beginning in the early 1930s for convenience. The spice mix typically includes a blend of cinnamon, nutmeg, ginger, allspice and cloves.

Pumpkins and pumpkin spice are now synonymous with fall in America. Pumpkin spice flavoring is used in candles, marshmallows, coffees, lotions, yogurts, pretzels, cookies, milk and many other products.

While pumpkin spice is available in one form or another all year long, sales of pumpkin-spiced products increase exponentially in the fall. The pumpkin spice craze is so popular that the start of the pumpkin spice season is a couple of months before the pumpkins themselves are even ready to harvest in October.

Pumpkin excursions

Americans continue to wholeheartedly embrace pumpkins today. Pumpkins in production are typically hand-harvested as soon as they mature, when the skins are hard enough to not be dented when you press it with your thumb.

Children often take field trips to pumpkin patches to pick their own. With the growing popularity of agritourism, many farmers are letting the customers go into the field and pick their own, getting more dollars per pumpkin than farmers could get by selling through the markets. Customer harvesting also reduces labor costs, produces immediate profits and builds community relationships.

In addition, farmers often combine the you-pick experience with other sources of income: corn mazes, hay rides, petting zoos and more. The customers get fresher fruit, enjoy a fun and educational activity and support the local economy.

This year you could get pumpkin spice flavors across the United States by late August, and the industry started promoting pumpkin spice season in July. Because fall has the right conditions for pumpkin picking, the season will keep its hold on pumpkin spice flavor, and consumers will continue to eagerly await its return each year.

At the ESMO Congress 2025 in Berlin, Dr. Joseph Tintelnot presented the interim analysis of the phase II PHERFLOT/IKF-053 trial (AIO STO 0321), an open-label, multicenter study evaluating whether adding pembrolizumab (anti-PD-1) and trastuzumab (anti-HER2) to perioperative FLOT chemotherapy (5-FU, leucovorin, oxaliplatin, docetaxel) could improve outcomes for patients with HER2-positive localized esophagogastric adenocarcinoma (EGA). Conducted by the AIO Study Group in Germany, this investigation explores the integration of immune- and targeted-therapy principles into a curative-intent treatment paradigm.

Background

For advanced or metastatic HER2-positive EGA, the combination of fluoropyrimidine-platinum chemotherapy with pembrolizumab and trastuzumab is already a standard of care, based on the positive results of the KEYNOTE-811 study. In localized disease, however, perioperative FLOT remains the preferred backbone due to its proven survival advantage over older ECF-based regimens. The PHERFLOT trial was designed to determine whether adding dual HER2 and PD-1 blockade could deepen pathological responses and potentially improve long-term survival without compromising surgical feasibility.

Study Design

PHERFLOT (NCT05504720) is a randomized, open-label, exploratory phase II study enrolling patients with resectable, HER2-positive localized EGA. The co-primary endpoints are 2-year disease-free survival and pathological complete response (pCR). Secondary objectives include safety, progression-free survival, objective response rate, and translational biomarker analyses, such as HER2 expression and PD-L1 combined positive score (CPS).

Patients received standard FLOT chemotherapy combined with pembrolizumab and trastuzumab in both the neoadjuvant and adjuvant settings, followed by curative-intent resection. The current report summarizes baseline characteristics, pathological outcomes, safety, and preliminary translational findings.

Results

Between March 2023 and May 2024, 31 patients were enrolled across multiple German centers. The median age was 65 years, and most had an ECOG performance status of 0 or 1. The majority of tumors arose at the gastroesophageal junction (77%), while a smaller proportion involved the stomach proper. HER2 overexpression was confirmed by immunohistochemistry, with 80.6% scoring 3+. PD-L1 CPS was ≥1 in 85% and ≥10 in half of evaluated cases, reflecting a generally inflamed tumor phenotype.

Thirty patients proceeded to R0 resection, and 70% experienced no postoperative complications, underscoring the feasibility of combining immune and targeted agents with intensive triplet chemotherapy. The pCR rate reached 48.4% (15 of 31), meeting the co-primary endpoint and far exceeding historical FLOT-alone benchmarks of roughly 15–20%. When subtotal responses were included, two-thirds of patients (67.8%) achieved major regression.

Twenty-one of 31 patients continued beyond perioperative therapy, corresponding to a feasibility rate of 67.7%.

The safety profile was consistent with expectations, except for an increased incidence of Grade 3 diarrhea (38.7%) and a higher re-operation rate (26.7% vs. 10% reported in FLOT4). The most frequent treatment-related events included diarrhea, weight loss, and hematologic toxicities such as neutropenia and anemia. The median hospitalization time was 14 days (vs 15 days in FLOT4), and no 30-day postoperative mortality occurred, confirming the acceptable perioperative safety of the regimen.

Translational Findings

Initial biomarker analyses suggest that PD-L1 expression may correlate with the depth of response, though patient numbers remain small. Ongoing translational work will explore the interaction between HER2 signaling, immune activation, and tumor regression, including immune-cell infiltration and circulating tumor DNA (ctDNA) kinetics. These data may ultimately clarify which subgroups derive the greatest benefit from the triplet combination.

Notably, higher pathological complete response rates were observed in patients with PD-L1 CPS ≥10 (63.6%) and in those with HER2 3+ expression (52%), indicating enhanced treatment sensitivity in these biomarker-enriched subgroups.

You can read the full abstract here.

Conclusions

The interim findings from PHERFLOT/IKF-053 demonstrate that combining pembrolizumab and trastuzumab with perioperative FLOT is feasible, tolerable, and highly active in localized HER2-positive esophagogastric adenocarcinoma. With nearly half of patients achieving complete pathological response and two-thirds achieving major regression, the regimen shows clear biological synergy and potential superiority over current standards.

The long-term results—particularly the 2-year disease-free survival data—will determine whether this intensified perioperative strategy can establish a new benchmark for this molecularly defined subgroup. If confirmed, PHERFLOT could represent a major step toward incorporating immunotherapy and HER2-targeted treatment into curative pathways for upper-GI cancers.

You Can Also Read MATTERHORN Trial at ESMO 2025: Durvalumab Plus FLOT in Resectable Gastric and GEJ Adenocarcinoma by OncoDaily

At a time when artificial intelligence is transforming industries across the globe, Cornell Engineering alumnus Jason Erdell ’95 returned to campus Oct. 17 to offer students a candid look at how to thrive in a time of rapid technological change.

Erdell, chairman and CEO of MDpanel, delivered his talk as part of the Mei-Mei Wei and Amy Cheng Distinguished Lecture Series, which brings accomplished alumni back to campus to share their insights on leadership, innovation and the future of engineering.

Erdell’s path since graduating from Cornell’s School of Operations Research and Information Engineering has taken him through Silicon Valley, management consulting and the private equity world. Today, he leads MDpanel, a company that uses AI, machine learning and data science to transform the delivery of medical opinions for insurers and healthcare organizations.

“Cornell taught me rigor,” he said. “It may not feel like it at the time, but that grit, that ability to struggle through a hard problem, is one of the greatest advantages you’ll carry forward.”

Before MDpanel, Erdell served as CEO of Aspirion, where he led similar AI-driven innovations in reimbursement services for major health systems. Across three decades of experience at the intersection of health care, technology and finance, he has focused on modernizing a system he calls “one of the most inefficient and complicated in the world.”

Erdell began his talk by reflecting on the extraordinary pace of AI development and the implications for productivity and work. “If you look at what’s happening right now,” he said, “the level of productivity increase that AI is driving is astronomical. The prosperity that’s going to come from it is immense.”

Comparing the current AI boom to the dawn of the internet, he argued that the stakes are even higher today. “When I was leaving Cornell, the web was just emerging. That was a huge wave of innovation, but this one is far bigger.”

Still, Erdell urged caution and reflection. AI, he said, may ultimately force society to rethink the very concept of work.

“There could come a point where the idea of a traditional job doesn’t exist anymore,” he said. “So what differentiates us as humans? Adaptability, creativity and continuous learning.”

Erdell organized his talk around what he called his three “bubbles” of growth: comfort, competency and innovation, with each representing a key to career success in an AI-driven world.

Expanding your comfort bubble

Erdell encouraged students to “embrace the struggle,” citing his own decision to leave consulting for an unexpected role at Gap, Inc.

“I knew nothing about fashion,” he admitted. “But I learned how to influence and/ or lead creative people and make decisions driven by empathy, not just logic.”

Expanding your competency bubble

In a world where entire professions can vanish overnight – “cartographers, for example,” Erdell said – breadth of skill is insurance against obsolescence.

“Don’t just go deep, go wide,” he advised. “The more competencies you have, the more adaptable you’ll be when the world shifts.”

Finding innovation bubbles below the surface

Rather than chasing the biggest, most obvious markets, Erdell argued that innovators can often find success by applying proven ideas in overlooked sectors.

“You don’t have to invent the next AI chip,” he said. “You can take what’s already working and apply it where others aren’t looking. For me, that’s health care administration, an industry that’s lagging, but full of opportunity.”

Throughout the lecture, Erdell emphasized the importance of lifelong learning and resilience.

“My life has been a beautiful collection of failures,” he said. “It’s through failure and discomfort that you grow.”

He urged students to take advantage of Cornell’s breadth, including its liberal arts courses, business law electives and cross-disciplinary environment, as a way to build flexibility of thought.

“You’re building yourself as an asset,” he said. “Don’t stop learning after you leave here.”

As a final takeaway, Erdell shared one of his company’s guiding principles – borrowed, he said, from the Mayo Clinic: “Think big, start small, move fast.”
“Focus on solving big problems,” he explained, “but start with the smallest viable step. Get your idea into the world, see how it behaves and iterate quickly.”

The talk ended with a Q&A that ranged from generative AI applications to the ethical use of technology. Erdell’s message to students was both pragmatic and optimistic: “AI will change everything,” he said. “But the people who succeed will be those who stay curious, keep learning and aren’t afraid to adapt.”

The Mei-Mei Wei and Amy Cheng Distinguished Lecture Series celebrates Cornell Engineering alumni whose work exemplifies leadership, innovation and impact across diverse industries.

Chris Dawson is a communications coordinator for Cornell Engineering.

China has banned exports of Nexperia’s finished products, which are widely used in car parts, in response to the Netherlands seizing control of the company.

German car parts supplier Bosch is preparing to furlough staff at its Salzgitter plant if a trade dispute between China and the Netherlands over Dutch chipmaker Nexperia is not resolved soon, amid mounting concerns in Europe’s beleaguered car industry.

Bosch and other suppliers are scrambling for alternatives after China banned exports of Nexperia’s finished products in response to the Netherlands seizing control of the company, whose Chinese owner Wingtech has been flagged by the United States as a possible national security risk.

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Because Nexperia’s chips are widely used in car parts, the standoff risks adding to problems for Europe’s carmaking sector on top of US tariffs and Chinese curbs on rare-earths exports.

“We are currently doing everything we can to serve our customers and avoid or minimise production restrictions,” a Bosch spokesperson said in an emailed statement to the Reuters news agency.

“We have not yet made any adjustments to working hours at our German locations, but are preparing to do so, particularly in Salzgitter,” she said, adding that potential furlough measures were being prepared at the plant.

Salzgitter is Bosch’s lead plant for motor control units for combustion and electric vehicles, and employs about 1,400 staff.

Earlier on Friday, Volkswagen said it had secured production in Germany for the coming work week across the group, which includes the core VW brand and luxury subsidiary Porsche.

“In view of the dynamic situation, however, short-term impacts on the production network of the Volkswagen Group cannot generally be ruled out,” a spokesperson said.

Worsening situation

BMW and Mercedes have also warned that their supplier networks are affected.

A regional representative of Germany’s IG Metall union warned on Friday of a worsening situation.

Some automotive suppliers are already seeing “severe difficulties” and have started to announce furlough schemes for workers, Horst Ott, IG Metall district manager in the southern state of Bavaria, said at an industry event in Munich.

He did not mention any companies by name.

Bosch said it was drawing on alternative suppliers and optimising inventories in its global production network in a bid to prevent production stoppages.

Most Nexperia chips are manufactured in Europe, but packaged in China.

Industry sources say switching suppliers is possible, with Infineon, NXP and Texas Instruments possible alternatives, but this takes time due to approval processes.

Auto industry bodies have called for a political solution.

Dutch Prime Minister Dick Schoof discussed the situation with other European leaders during an EU summit in Brussels this week.

The FDA has granted breakthrough therapy designation to zenocutuzumab-zbco (Bizengri) for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma harboring a NRG1 gene fusion.¹

The designation was based on findings from the phase 2 eNRGy trial (NCT02912949), updated results from which were presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets. The data will also serve as the basis for the 2026 filing of the agent’s supplemental biologics license application to the FDA.

“NRG1 fusions represent a rare but actionable driver in cholangiocarcinoma, and the data from the eNRGy trial continue to highlight the potential of zenocutuzumab to offer meaningful clinical benefit for these patients. I’m honored to present these findings at AACR-NCI-EORTC, where we can advance the dialogue around targeted therapies in hard-to-treat cancers,” Alison M. Schram, MD, principal investigator of the eNRGy trial and associate attending physician at Memorial Sloan Kettering Cancer Center in New York City, New York, stated in a news release.

What was the design of the ongoing eNRGy trial?

The global, multicenter phase 1/2 eNRGy trial was designed to evaluate zenocutuzumab in patients with advanced NRG1-positive solid tumors, including cholangiocarcinoma, pancreatic ductal adenocarcinoma, and non–small cell lung cancer (NSCLC).² To be eligible, patients had to be at least 18 years of age and have received a diagnosis of an advanced or metastatic solid tumor with a NRG1 gene fusion. Patients also had to be previously treated or unable to receive standard therapy and have an ECOG performance status between 0 and 2.

All patients received 750 mg of zenocutuzumab intravenously over a 2-hour infusion every 2 weeks until progressive disease or unacceptable toxicity. Tumor assessment was performed every 8 weeks. The first infusion of zenocutuzumab was administered over 4 hours and accompanied by premedication with antipyretics, antihistamines, and glucocorticoids to minimize the incidence of infusion-related reactions (IRR).

What data were presented at the 2025 AACR-NCI-EORTC meeting?

The cholangiocarcinoma cohort served as the focus of the AACR-NCI-EORTC presentation. A total of 22 patients were enrolled in the safety analysis cohort, 3 of whom were excluded from the primary efficacy cohort (n = 19) due to prior HER3-directed exposure and the presence of another oncogenic driver (n = 1).

The primary end point was investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary end points included duration of response (DOR), clinical benefit rate (CBR), and progression-free survival (PFS) per investigator assessment, as well as DOR, ORR, and PFS per blinded independent central review, and safety.

The median age was 57.5 years (range, 23-82), and most patients were women (55%). ECOG performance status was predominantly 0 (63%), and anatomic location was largely intrahepatic (82%). Most patients also had stage IV disease at screening (95%) and had discontinued treatment (82%) because of progressive disease (68%).

With respect to treatment history, 89% of patients received prior systemic therapy, which included chemotherapy (84%), immunotherapy (16%), anti-VEGF therapy (5%), and transarterial chemoembolization (5%). The median number of prior treatment lines was 1 (range, 0-4): 0 (11%), 1 (47%), 2 (26%), 3 (5%), and 4 (11%). The time since metastatic diagnosis was 9.3 months (range, 1.6-34.2).

The results indicated that the investigator-assessed ORR was 37% (95% CI, 16%-62%) and the CBR, defined as partial or complete response or stable disease for at least 24 weeks, was 58% (95% CI, 33%-80%). The median duration of treatment was 9.2 months (range, 1.0-31.0) and the median time to response was 1.9 months (range, 1.2-5.5). The median DOR was 7.4 months (range, 3.6-11.1).

The median PFS was 9.2 months (95% CI, 3.9-11.4); the estimated 6- and 12-month PFS rates were 64.7% (95% CI, 37.7%-82.3%) and 21.8% (95% CI, 5.5%-45.0%), respectively. At a median follow-up of 15.2 months (range, 1.2-34.1), the median overall survival (OS) was not evaluable ([NE] 95% CI, 16.1-NE); the estimated 12- and 18-month OS rates were 80.5% (95% CI, 50.6%-93.3%) and 67.1% (95% CI, 30.5%-87.5%), respectively.

“Patients with cholangiocarcinoma face an aggressive disease with limited standard therapy options,” Juan W. Valle, MBChB, MSc, FRCP, chief medical officer of the Cholangiocarcinoma Foundation, added in the news release.¹ “The eNRGy trial results are encouraging, and they underscore how critical comprehensive molecular testing, notably tissue-based RNA next-generation sequencing [NGS], is to ensure that patients with rare drivers such as NRG1 fusions are identified and can potentially have access to targeted treatments.”

Among patients with evaluable CA 19-9 data (n = 16), all experienced a decline in serum levels, including a 50% or greater reduction in 68.8% (n = 11) of patients.² The median time to first 50% or greater reduction was 1.0 month. Among patients with evaluable CEA data (n = 11), 63.6% (n = 7) experienced a 50% or greater reduction, with a median time of 1.0 month for the first 50% or greater reduction.

The safety profile was consistent with that of the overall eNRGy trial population. Most treatment-emergent adverse effects (TEAEs) were grade 1 or 2: anemia (all grade, 45%; grade 3/4, 14%), diarrhea (all grade, 41%; grade 3/4, 0%), hypomagnesemia (all grade, 27%; grade 3/4, 9%), abdominal pain (all grade, 27%; grade 3/4, 5%), cough (all grade, 27%; grade 3/4, 0%), fatigue (all grade, 27%; grade 3/4, 0%), nausea (all grade, 27%; grade 3/4, 0%), alanine aminotransferase increase (all grade, 23%; grade 3/4, 5%), and gamma-glutamyltransferase increase (all grade, 9%; grade 3/4, 9%).

Five patients (23%) experienced serious adverse effects, none of which were treatment related. No patients discontinued therapy because of treatment-related toxicity, nor did grade 5 TEAEs occur. One patient experienced grade 3 or greater treatment-related anemia, and two cases (9%) of grade 1/2 IRR occurred.

“In December 2024, zenocutuzumab received accelerated approval³ for the treatment of adults with advanced unresectable or metastatic NSCLC and pancreatic adenocarcinoma harboring a NRG1 gene fusion with disease progression on or after prior systemic therapy.¹ The new data from the eNRGy trial highlight the potential of zenocutuzumab-zbco as a promising treatment option for patients with NRG1 fusion–positive cholangiocarcinoma,” Pritesh J. Gandhi, PharmD, chief development officer of Partner Therapeutics.

“With the growing number of genomic alterations and gene fusions that are now actionable, it is imperative that oncologists order upfront tissue-based RNA NGS to ensure that gene fusions, of which NRG1 is just one, are not missed,” Gandhi concluded.

References

1. Zenocutuzumab-zbco granted FDA breakthrough therapy designation for NRG1+ cholangiocarcinoma; data highlighting potential of zenocutuzumab-zbco in NRG1+ cholangiocarcinoma to be presented at AACR-NCI-EORTC. News release. Partner Therapeutics, Inc. October 23, 2025. Accessed October 24, 2025. https://www.partnertx.com/zenocutuzumab-zbco-granted-fda-breakthrough-therapy-designation-for-nrg1-cholangiocarcinoma-data-highlighting-potential-of-zenocutuzumab-zbco-in-nrg1-cholangiocarcinoma-to-be-presented-at-aacr-nci/
2. Schram AM, Cleary JM, Arnold D, et al. Zenocutuzumab efficacy and safety in advanced NRG1+ cholangiocarcinoma: analysis from the phase 2 eNRGy trial. Presented at: AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics; October 22-26, 2025; Boston, Massachusetts. Abstract A102.
3. FDA grants accelerated approval to zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma. FDA. December 4, 2024. Accessed October 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zenocutuzumab-zbco-non-small-cell-lung-cancer-and-pancreatic