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Sunshine, smiling faces, and great anticipation for the 36th BMW International Open.

+++ Pro-Am tournament featuring football, winter sports, and film
stars +++ Pros excited for a special week on the tour calendar +++
Martin Kaymer: “I’m proud that we have such a fantastic event in
Germany” +++ Quotes and images from Wednesday +++ All press
conferences available for download as video +++

Munich. Excitement was palpable today at Golfclub
München Eichenried ahead of the tournament rounds of the
36^thBMW International Open (July 2–6, 2025) – among
amateurs, who got to play a memorable round with a pro in the Pro-Am
tournament, among professionals set to compete for one of the most
coveted titles on the DP World Tour starting tomorrow, and among fans,
who witnessed a host of celebrities on the course.

The only German winner in the tournament’s history, Martin Kaymer,
teed off alongside “Golden Goal” hero Oliver Bierhoff, former national
player Tim Borowski, and coach Ralph Hassenhüttl (AUT). A “golden
trio” was formed by six-time Olympic luge champions Tobias Wendl and
Tobias Arlt (doubles), together with Michael Greis, three-time Olympic
biathlon champion. Ice hockey was also well represented by NHL stars
Moritz Seider and Tim Stützle, as well as national team player
Maximilian Kastner. Former world-class tennis player and record winner
of the BMW Open in Munich, Philipp Kohlschreiber, also proved his
skills with a golf club.

From the film industry, actors Kai Wiesinger and Kostja Ullmann, as
well as director, screenwriter, and producer Florian Gallenberger,
joined the event. A native of Munich, Gallenberger won an Oscar in
2001 in the Best Live Action Short Film category. Celebrity
photographer Paul Ripke also showed his talents on the championship course.

The first round of the BMW International Open starts on Thursday at
7:30 a.m., with three-player groups teeing off from Tee 1 and Tee 10.

Quotes from Wednesday.

Martin Kaymer (GER): “The people you work with
make all the difference. You can really feel how much passion and
attention to detail everyone at BMW puts in. That makes it very
pleasant for us players. It’s a luxury on the DP World Tour to be able
to play here. I’m always grateful and, as a German, proud that we have
such a fantastic event. It’s a joy to come here every time.”

Marcel Siem (GER): “I don’t usually say this
before a tournament, but I finally want to win here. That’s always my
goal when I come. I’ve been coming here since I was a kid and even
became club champion. No one knows the course better than I do. I want
to win and put on a great show.”

Ewen Ferguson (SCO): “I’ve always loved coming
to this tournament. Munich is such a beautiful city. It’s always a
pleasure to be here. The course, the event, the infrastructure, the
player’s lounge, the food—everything is fantastic. Coming back as the
defending champion and seeing my face around the venue is a great feeling.”

Tobias Arlt (GER): “It’s just awesome to be part
of the BMW International Open. It’s incredibly beautiful to play in
this weather. Enjoying the Pro-Am with the pros and learning from them
is amazing.”

Tobias Wendl (GER): “It’s so impressive to see
what the professionals can do, but it’s also great to see the people.
We’re usually alone on the golf course. That’s why it’s great to see
how many people are passionate about the sport.”

Michael Greis (GER): “The pros are just insane.
It really shows how far away we amateurs are. But it’s incredibly fun.
An absolute blast.”

Luke Donald (ENG): “It’s great to be around the
players and to interact with them as much as possible. That’s a very
important and meaningful part of my job – to talk to them and see how
they play. Playing the course yourself gives you a better
understanding. And when someone posts a strong score, you’ve seen it
firsthand. I enjoy a healthy mix of watching tournaments on TV and
playing a few myself—especially the BMW International Open.”

We have recorded today’s press conferences in full length as
video files. You may use these recordings free of charge for
editorial purposes. You can find the files, along with all other
recordings from the 2025 BMW International Open, here:
https://nextcloud.bs-plus.de/s/gfJoH7wsrrzawHT

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July 2, 2025
“It’s the Holy Grail” Alex Springer on impact.com’s Product Roadmap and AI

At iPX London, we caught up with impact.com’s Senior Director, AI and Marketplace Products, Alex Springer, to learn more about the platform’s product roadmap this year – before he got the chance to explore the rest of London’s Science Museum.

Springer relayed all of the new features coming to impact.com throughout a session earlier in the day.

There is a wealth of new additions. Some of the highlights include: a mobile app; a Chrome extension; an intuitive AI chatbot; deeper programme analysis; SPOT Commerce (a retail media booster); Real Time Search; and agentic AI tools.

Of the new features, Springer pinpoints advanced programme recommendations as the most revolutionary.

“The scale at which we can process data now has allowed us to start to understand some very unique things that we couldn’t before,” he says. “If I can deterministically tell you that an audience who reads about this stuff eventually goes and buys this stuff – that’s huge. That’s the Holy Grail. That’s what we’ve been looking for across the marketing industry.”

He continues, “It redefines demographic. I don’t care if you’re old or young, or from this country or that country. What we care about now is interest demographics. We’ve been using machine learning to be able to determine those links and surface them to people.”

We also discuss planning entire campaigns with natural language alone; scepticism and optimism around AI; and what impact.com has to offer affiliate marketers in today’s landscape.

Watch the full interview below.

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July 2, 2025
Air chief meets senior military, political leadership in landmark US visit – World

Pakistan Air Force (PAF) Chief Air Marshal Zaheer Ahmed Baber Sidhu held a series of high-level meetings with senior military and political leadership of the United States in a landmark visit to the country, it emerged on Wednesday.

Last month, Field Marshal Asim Munir became the first serving chief of army staff to have a face-to-face meeting with a sitting US president when he met Donald Trump for talks at the White House. The occasion also marked the first time a serving Pakistani army chief had been formally received at this level, without holding political office or governing under martial law. The two had discussed joint counter-terrorism efforts and expanding bilateral trade during their “cordial” meeting in Washington.

Today, PAF’s Directorate General of Public Relations (DGPR) said that in a “significant development” aimed at strengthening bilateral defence cooperation and advancing mutual interests, the air chief undertook an official visit to the US, adding that it was the “first by a serving PAF air chief in over a decade”.

It said the high-profile visit marked a “strategic milestone” in Pakistan-US defence cooperation and “proved instrumental in deepening institutional ties” in addition to addressing key regional and global security issues.

The DGPR said that at the Pentagon, the air chief called on US Air Force (International Affairs) Secretary Kelli L Seybolt and Chief of Staff of the US Air Force General David W Allvin.

“The discussions centred around advancing bilateral military cooperation, enhancing interoperability and exploring avenues of joint training and technology exchange. Chief of the air staff highlighted the historic and multifaceted relationship between Pakistan and US, particularly in the domains of defence and security cooperation.

“He reiterated his resolve to further enhance the existing ties in the realms of military-to-military cooperation and training between the air forces of the two countries. The two sides also agreed upon the continuation of high-level military engagements in future through senior-level interactions,” the DGPR said.

It said these interactions were deemed crucial for maintaining momentum in ongoing cooperative endeavours in the areas of joint training, operational exercises and military exchange programmes between the two nations.

At the US State Department, the air chief met Brown L Stanley from the Bureau of Political-Military Affairs and Eric Meyer from the Bureau of South and Central Asian Affairs. The DGPR said the meetings served as a forum to “underscore Pakistan’s constructive role in promoting regional stability, its firm commitment to counter-terrorism efforts and its nuanced perspective on the evolving geopolitical dynamics of South and Central Asia”.

As part of his engagements at Capitol Hill, the air chief held “substantive dialogues with prominent members” of the US Congress, including Mike Turner, Rich McCormick and Bill Huizenga.

“These interactions reinforced the importance of robust engagement in strengthening bilateral relations and provided a valuable opportunity to share Pakistan’s views on strategic challenges, regional security frameworks and the impact of emerging technologies on defence cooperation.

“Emphasising Pakistan’s status as a peace-loving nation, the air chief reaffirmed the country’s enduring sacrifices and notable operational achievements in the global war on terror, while also outlining Pakistan’s evolving security calculus in response to the rapidly shifting regional geopolitical landscape.”

The DGPR said the “landmark visit” not only reaffirmed PAF’s commitment to promoting regional and global peace, but also laid the groundwork for renewed institutional collaboration, strategic dialogue and enhanced interoperability between it and the US Air Force.

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July 2, 2025
Ancient Life Locked Arsenic Away To Survive Environmental Changes

A 3D image obtained by X-ray microtomography of a macroscopic multicellular organism dated to 2.1 billion years ago (Francevillian Basin, Gabon). Scale bar = 1 cm. Credit Arnaud Mazurier and Abderrazak El Albani.

Earth’s earliest life forms developed ways to survive the harmful effects of arsenic to cope with dramatic changes in their environment, a new study suggests.

The researchers found the complex life forms, called eukaryotes, stored arsenic inside special compartments within their cells, a strategy that helped neutralise the toxic poison.

Using advanced X-ray technology, the international team was able to detect and map arsenic within 2.1-billion-year-old fossils from the Francevillian Basin in Gabon.

The arsenic found in the fossils was not due to later contamination but part of a biological response to environmental stress, according to the team.

a Lobate fossil with imprint showing dispersed pyrite grains at the radial fabrics (RF) and coagulated pyrite towards the dome (D) (b). c Elongate fossil (E) in a matrix (M) with imprint surrounded by bacterial mat33 showing mainly coagulated pyrite crystals (d). e Tubular fossil (T) having an ovoid diameter filled with coagulated pyrite in a matrix (M) (f). g Pyritized abiotic concretion (C) found in the same location and containing massive pyrite (h). The diameter of the coin in (g) is 3.6 cm. Scanning electron microscope is used in back-scattered electron mode in b, d, f and h. It shows pyrite grains filling the specimens in a vertical transect — Nature Communications.

This is revealed by distinct patterns formed from the arsenic preservation process in the fossils when compared to structures left by non-living mineral structures; it is further evidence the fossils were once complex living organisms with more advanced cells, they argue.

Their study, published in Nature Communications, reshapes current understandings of how early life faced environmental challenges, highlighting the critical role adaptation played in the evolution of life.

“The ability to cope with arsenic was not something eukaryotes developed randomly,” said Dr Ernest Chi Fru, one of the paper’s co-authors and Reader at Cardiff University’s School of Earth and Environmental Sciences.

“It coincided with a period of significant environmental change, when oxygen levels in the Earth’s atmosphere first rose. This increase in oxygen also led to a rise in arsenate, a particularly toxic form of arsenic which competes with phosphate, a vital nutrient for all life, making Earth’s oceans a dangerous place.”

a Oxidized As—arsenate or As5+ (red dots) is released into the ocean by the chemical and oxidative weathering of the continental crust. b During life, As enters the cell, and is detoxified first by reduction to As3+ (c) then extruded by cell membrane transporters or sequestered in intracellular compartments (d). e After death and burial, As is released from intracellular bodies into a localized reduced environment rich in iron (purple dots) where sulfate (green dots) is reduced to sulfides (yellow dots). f Pyrite is formed by microbial sulfate reduction with As acting as a catalyzer of pyrite nucleation. g Arsenic is rapidly consumed in low environmental concentrations. h Pyrite growth led to As depletion away from the core — Nature Communications.

The study builds on the team’s previous work on the 2.1-billion-year-old Francevillian biota, which they argue appeared after a local underwater volcanic event brought a sudden surge of nutrients into a small, enclosed sea.

This nutrient boost helped these early life forms thrive locally, according to the team led by Université de Poitiers and Cardiff University.

Dr Chi Fru added: “We looked at the evolution of arsenic in the Francevillian basin’s seawater before and after the fossils. It was actually quite low in arsenic concentration at the time when these primitive eukaryotes evolved, leading us to think they should have lived there quite happily.

“However, the surprisingly high levels of arsenic stored in their bodies, revealed in our analysis, suggest that they were extremely sensitive to even low levels of arsenic in seawater.”

These organisms later became extinct when volcanic activity returned to the area, and oxygen levels in the seawater dropped, according to the team.

They say their disappearance suggests the ability of complex life to protect itself from toxic substances like arsenic, by safely storing it inside cells, may have evolved more than once in Earth’s history.

“All living things have ways to protect themselves from arsenic, which is toxic to life,” Dr Chi Fru said.

“In the ocean, tiny plankton near the surface — the same ones that make about half the oxygen in the air we breathe — are always working to get rid of arsenic from their bodies. They can’t avoid it because arsenic is naturally in the water, and their cells can’t easily tell the difference between arsenate and phosphate, a nutrient they actually need. This was true even in ancient times, just like it is today.

“We know these ancient organisms went extinct, so the way modern life handles arsenic didn’t come directly from them.”

The paper, ‘A battle against arsenic toxicity by Earth’s earliest complex life forms’, is published in Nature Communications. (open access)

Astrobiology

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July 2, 2025
Lipid Receptor Checkpoint Found to Drive T-Cell Exhaustion – Inside Precision Medicine
1. Lipid Receptor Checkpoint Found to Drive T-Cell Exhaustion Inside Precision Medicine
2. Lipids rewire T cell exhaustion nature.com
3. Newly discovered target may re-energize exhausted immune cells in the fight against cancer News-Medical
4. The prostacyclin receptor PTGIR is a NRF2-dependent regulator of CD8 nature.com
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July 2, 2025
Chairperson BISP Senator Rubina Khalid strongly condemns Bajaur bomb blast

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ISLAMABAD, Jul 02 (APP): Chairperson Benazir Income Support Programme (BISP), Senator Rubina Khalid has strongly condemned the recent terrorist attack in Bajaur district, expressing deep sorrow over the loss of precious lives in the tragic incident.

In a statement, Senator Rubina Khalid said, “I strongly condemn the terrorist attack in Bajaur. It is heartbreaking to learn about the martyrdom of Assistant Commissioner Nawagai, Tehsildar, and other officials in this heinous act.”

She asserted that terrorists are the enemies of peace and stability and are determined to tarnish Pakistan’s image. “These elements do not want to see Pakistan prosper. But the people of Pakistan have always raised their voices against terrorism,” she added.

Senator Rubina Khalid paid rich tribute to the Pakistan Army, stating that the armed forces have always bravely confronted terrorism and safeguarded the nation with unmatched courage.

“I stand in solidarity with the families of the martyrs in this hour of grief and pray for their strength and patience. The sacrifices of our martyrs will always be remembered,” she emphasized.

Senator Rubina Khalid also prayed for the elevation of the ranks of the martyrs and extended heartfelt condolences to their bereaved families.

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July 2, 2025
Tinder Users Must Start Logging In With Their Faces

California Tinder users will find a new feature when they open up the dating app on July 7: A mandatory Face Check on their phones will be required before they can log into their profiles.

The Face Check step will begin with a new request to record a video of your face, a more casual version of setting up Apple’s Face ID login. Tinder will then run checks comparing your face data to your current profile pics and automatically create a small face badge for your profile. We know just how it works, because Tinder has already launched the feature in Canada and Colombia.

The technology, powered by FaceTec, will keep biometric data of the user’s face in encrypted form but discard the scanning video for privacy. Tinder will be able to use the face data to detect duplicate accounts, in an effort to cut down on fake profiles and identity theft.

Tinder’s facial recognition rollout is also made to prevent catfishing, or people pretending to be someone else on Tinder to scam or blackmail them. But that also points to a deeper problem on the rise in dating apps — a growing number of bots, many controlled by AI, are designed to glean personal information or fool users into scammy subscriptions, among other problems.

Don’t confuse the more in-depth Face Check with the earlier Tinder photo verification feature.

Tinder

Tinder’s working against these bots on several fronts, including this Face Check push as well as ID Check, which requires a government-issued ID and other types of photo verification.

There’s no word yet on when Face Check will move beyond California.

The dating app also recently released a feature in June to enable double-dating with your friends, which Tinder reports is especially popular with Gen Z users. If you’re worried about the latest hazards on Tinder, we have guide to safety practices.

A representative for Tinder did not immediately respond to a request for comment.

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July 2, 2025
The Best Color-Changing pH Lip Balms and Lip Oils, Tested by Editors

If you purchase an independently reviewed product or service through a link on our website, WWD may receive an affiliate commission.

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Top Color-changing Lip Products of 2025

There’s a particular kind of magic in watching a sheer lip product morph into your perfect pink — especially when it happens in real time, on your own smile. That might be why color-changing lip oils, balms, and glosses have surged in popularity in the last year, crowding both social media feeds and Sephora’s new releases landing page.

Take, for instance, the viral moment when Sabrina Carpenter swiped on Prada’s Moisturizing Lip Balm in Astral Pink in a TikTok video last June that’s since been viewed over 50 million times. The tinted lip balm‘s cameo caused it to sell out in short order, creating a new level of demand for a cosmetic category that isn’t exactly new (beauty historians will recall brands like Tangee releasing 1.0 versions of pH lip balms nearly a century ago).

Much of the modern-day appeal lies in the transformation itself. Color-changing lip glosses, balms, and lip oils are inherently satisfying to watch — especially on platforms like TikTok, where visual payoff is everything. But beyond the aesthetic thrill, these products promise a more personalized experience.

At their core, color-changing lip products rely on pH-reactive technology: In basic terms, these formulas contain ingredients that adjust their hue based on the natural acidity of your skin. The result? A just-for-you tint that’s designed to be bespoke to you — at least in theory. In practice, most pH lip balms and oils tend to skew toward the shade of a cool-toned pink lipstick. The differentiator, then, becomes texture, shine, and overall feel.

We tested over a dozen of the most talked-about options to find the best pH lip balm formulas on the market. Whether you’re after a high-shine gloss that changes color with your pH, a juicy lip oil that delivers sheer color and serious moisture, or something in between, these three picks stood out for their finish, wear, and just-right flush.

Sign up for WWD Shop’s newsletter to get the scoop on the best in beauty and style with in-depth reviews of exciting new releases and buyer’s guides to find the products you need to try ASAP.

Prada Moisturizing Lip Balm in 001 Astral Pink

Two WWD Shop editors swear by Prada’s lip color collection — we rate the products as luxury beauty accessories that are well worth the investment for their packaging, shade range, and lip-softening formulation.

This Prada pH lip balm is one of the subtler color-changing products you can find on the market, in a good way. Rather than overpowering your pout in a fuchsia color, it acts as more of a filter on the lips that blurs fine lines and adds a touch of oomph to your natural lip color.

Price upon publish date of this article: $50

TirTir Water Mellow Lip Balm in 01 Icy Blue

A low-stakes entry point to the color-changing lip balm category, TirTir’s Water Mellow Lip Balm is the best affordable pH lip treatment we tested. Where some color-changing balms take a few seconds to fully transform on your lips, this one creates a custom tint immediately upon application — one that errs on the punchy-pink side, if you opt for our favorite Icy Blue shade (shown). Our testers found that the product requires a few swipes for even application, but otherwise, you’d never know that it’s priced under $20.

Price upon publish date of this article: $15

WWD/ Claire Sullivan

Tarte Maracuja Juicy Lip pH Powered Plumping Shift Lip Balm

For max shine and staying power, go with Tarte’s color-changing lip treatment. The product gives the juicy finish of a great gloss while subtly plumping your lips — and the custom color you’ll get is more pigmented than similar ones we tried. Our testers found that the tint could last for a full three hours without needing a touch-up; after that, an additional swipe is helpful to facilitate even fading.

Price upon publish date of this article: $27

More pH Lip Balms & Lip Oils to Try

Milk Makeup Cooling Water Jelly Tint in Phreeze

Our editors love the watercolor effect of Milk Makeup’s Cooling Water Jelly Tints — rather than color that you need to carefully apply, you can be generous with the product’s application and blend it with a makeup sponge or clean fingertips for a flawless flush of color. The color-changing Phreeze shade starts out as a coral peach then fades to a cool-toned pink in a few seconds. Slough your smile with a lip scrub before using it for best results.

Price upon publish date of this article: $24

Winky Lux Flower Balm

Another affordable pick for those who want to test out a pH lip balm without a huge commitment, Winky Lux’s Flower Balm is a favorite, available in three translucent shades that shift pink upon application. We found it to be best for a touch of color, but don’t expect anything transformative in terms of hydration or shine.

Price upon publish date of this article: $17

Haus Labs Phd Hybrid Lip Oil

While we found pH lip balms to be easiest to apply, Haus Labs makes the best color changing lip oil for those who prefer a syrupy, silky texture without a lick of stickiness. The product is one of few in its category that actually nourishes the lips, too, courtesy of its softening prickly pear oil.

Price upon publish date of this article: $26

Why Trust WWD

Since 1910, WWD — often referred to as “the fashion bible” — has been the leading industry voice of authority for senior executives in the global women’s and men’s fashion, retail and beauty communities, while also informing the consumer media that cover the market. Today, WWD’s breaking news and trend coverage continues to be a trustworthy resource for both fashion insiders and consumers alike. Our shopping editors continue to uphold WWD’s editorial standards and values with quality, expert-backed product selections. Learn more about us here.

Meet the Author

Claire Sullivan is a contributing commerce editor for WWD and Footwear News, where she writes and edits beauty, fashion, and lifestyle stories. She has over eight years of experience as a writer and editor for national media outlets including Martha Stewart Living, Martha Stewart Weddings, InStyle, and Byrdie. She’s tested hundreds of products during her time as an editor, so she’s well-versed in selecting the products that make a meaningful difference in your skin and hair. Sullivan contributed to product testing and reporting to write this article on the best color-changing lip balms and oils.

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July 2, 2025
3 Things You Should Know About Targeting NRG1 and Rare Drivers in Pancreatic Cancer

RELEASE DATE: June 1, 2025
EXPIRATION DATE: June 1, 2026

LEARNING OBJECTIVES

Upon successful completion of this activity, you should be better prepared to:

• Evaluate the role of mutations in NRG1 and other genetic alterations in diagnosis and management.

• Discuss current guidelines and treatment recommendations for the management of patients with advanced pancreatic cancer.

• Analyze clinical trial data to inform the selection of emerging therapeutic agents for advanced pancreatic cancer.

• Apply strategies to optimize molecular testing algorithms using diverse testing modalities in advanced pancreatic cancer.

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Physicians’ Education Resource^®, LLC, designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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This activity is supported by an educational grant from Partner Therapeutics, Inc.

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This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this activity is for accredited continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER^® or any company that provided commercial support for this activity.

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To date, 32 genes have been identified as frequently mutated in pancreatic ductal adenocarcinoma (PDAC).¹ However, less than 10% of patients are eligible for an FDA-approved targeted therapy, highlighting the need for the development of novel therapeutics.² Here are 3 things you should know about molecular testing and personalized strategies in pancreatic cancer.

1 RNA testing is critical to identify actionable gene fusions in PDAC.

NCCN guidelines recommend tumor molecular profiling in cases of metastatic PDAC.³ RNA-based next-generation sequencing (NGS) is preferred to DNA-based NGS for detecting fusions in genes like ALK, NRG1, NTRK, ROS1, FGFR2, and RET. These fusions are enriched in the 5% to 10% of patients with KRAS wild-type PDAC, a molecular profile more often found in patients younger than 50 years.⁴ NGS using tumor tissue is preferred to blood-based assays, according to NCCN guidelines.³ Liquid biopsy can be performed concurrently with tissue testing or used when adequate tissue is unavailable.

RNA-based NGS can detect structural variants of gene fusions, which may inform the potential efficacy of targeted therapies.⁵ Since RNA sequencing encompasses only exons after splicing, this technique can overcome the technical challenges of excessive sequencing or misaligned reads when DNA-based NGS is used on genes with long or repetitive introns (Figure 1).⁶ In a heterogeneous tumor in which the gene fusion is present only in some cells, RNA-based NGS can detect the alteration if it is highly expressed.

FIGURE 1.RNA-based NGS May Overcome Limitations of DNA-Based Testing⁶

2 The first NRG1-targeted therapy is approved for advanced or metastatic PDAC.

NRG1 fusions are found in approximately 1% of solid tumors, most commonly in patients with mucinous adenocarcinoma of the lung and KRAS wild-type PDAC.⁷ These altered proteins consist of the EGF-like domain of NRG1 attached to the transmembrane domain of various fusion partners. This construct enables constitutive binding and activation of the HER3 receptor, activating RAS and the MAPK and PI3K signaling pathways.

Zenocutuzumab is a HER2×HER3 bispecific antibody that inhibits NRG1 binding.⁸ In the phase 1/2 eNRGy trial (NCT02912949), zenocutuzumab demonstrated an overall response rate (ORR) of 30% (95% CI, 23%-37%) in 158 patients of all tumor types with NRG1 fusions.⁹ The response rate in 33 patients with PDAC was 42.4% (95% CI, 25.5%-60.8%), including 1 complete response and 13 partial responses (Figure 2).¹⁰ The median progression-free survival in the overall population was 6.8 months (95% CI, 5.5-9.1 months).⁹ The most common treatment-related adverse events (TRAEs) were diarrhea (18%), fatigue (12%), and nausea (11%). Infusion-related reactions occurred in 14% of patients. Based on results from the eNRGy study, zenocutuzumab received accelerated approval from the FDA as a second-line systemic therapy to treat advanced, unresectable, or metastatic PDAC harboring an NRG1 gene fusion.¹¹

FIGURE 2. Response to an NRG1 Inhibitor in Pancreatic Adenocarcinoma¹⁰

3 Ongoing investigations are evaluating numerous other emerging targets of interest.

In addition to NRG1 fusions, 38.5% of KRAS wild-type PDAC tumors harbor other genetic alterations, including FGFR2 or FGFR3 fusions, ERBB2 (HER2) amplification, BRAF mutations, and RET fusions.⁴ Erdafitinib demonstrated an ORR of 30% (95% CI, 24%-36%) in patients of different tumor types harboring FGFR alterations in the single-arm, phase 2 RAGNAR trial (NCT04083976).¹² The ORR was 56% in patients with PDAC.

Combination dabrafenib and trametinib produced an ORR of 38% (95% CI, 22.9%-54.9%) in patients with solid tumors, lymphomas, or multiple myeloma whose tumors harbored a BRAF V600 mutation in the single-arm NCI-MATCH trial subprotocol H (NCT02465060).¹³ Of the 27 evaluable patients, the 1 patient with PDAC achieved stable disease. Combined use of dabrafenib and trametinib received accelerated approval to treat patients with unresectable or metastatic solid tumors, including PDAC, that harbor BRAF V600E mutations and who have progressed following prior treatment.¹⁴

Selpercatinib yielded an ORR of 43.9% (95% CI, 28.5%-60.3%) in patients with RET fusion-positive non-lung and non-thyroid solid tumors in the phase 1/2 LIBRETTO-001 basket trial (NCT03157128).¹⁵ The ORR was 44% in patients with PDAC. Selpercatinib received accelerated approval to treat adults with locally advanced or metastatic solid tumors, including PDAC, that harbor a RET gene fusion and who have progressed following prior treatment.¹⁶

The HER2-targeting antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (T-DXd) has not provided as much benefit in patients with PDAC. In the phase 2 DESTINY-PanTumor02 trial (NCT04482309) in patients with solid tumors overexpressing HER2 (immunohistochemistry [IHC], 3+ or 2+), the ORR was 37.1% (95% CI, 31.3%-43.2%) across all cohorts, but only 4.0% (95% CI, 0.1%-20.4%) in those with PDAC.¹⁷ Further investigation would be required to determine why this disease type is particularly resistant to T-DXd, but this agent is still approved for HER2 IHC 3+ PDAC under the tissue agnostic approval.

The TP53 Y220C mutation is the target of the first-in-class p53 reactivator PC14586.¹⁸ In the phase 1 portion of the phase 1/2 PYNNACLE trial (NCT04585750) at the highest dose of PC14586, the ORR was 46.2%. In 6 patients with PDAC, 4 achieved stable disease, and 1 achieved an unconfirmed partial response.

Claudin18.2 (CLDN18.2) is an emerging actionable target in many cancers, including PDAC.¹⁹ Therapeutics with various mechanisms of action are under investigation to exploit this target. IBI389 is a CLDN18.2×CD3 bispecific antibody evaluated in a phase 1 study (NCT05164458) in 64 previously-treated patients with CLDN18.2-positive PDAC.²⁰ The ORR was 30.4% (95% CI, 13.2%-52.9%), and the disease control rate was 69.6% (95% CI, 47.1%-86.8%). TRAEs of grade 3 or greater were reported in 54.7% of patients. Treatment was discontinued in 4.7% of patients due to TRAEs. Cytokine release syndrome is an AE of particular concern with IBI389, with grade 1 or 2 events occurring in 51.6% of patients.

Zolbetuximab is an anti-CLDN18.2 monoclonal antibody being tested against several tumor types and will be assessed in combination with gemcitabine/nab-paclitaxel (GN) vs GN alone as first-line therapy in patients with metastatic pancreatic cancer in a phase 2 study (NCT03816163).²¹ The primary end point is overall survival.

Key References

4. Singhi AD, George B, Greenbowe JR, et al. Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as biomarkers. Gastroenterol. 2019;156(8):2242-2253.e4. doi:10.1053/j.gastro.2019.02.037

6. Davies KD, Aisner DL. Wake up and smell the fusions: single-modality molecular testing misses drivers. Clin Cancer Res. 2019;25(15):4586-4588. doi:10.1158/1078-0432.Ccr-19-1361

9. Schram AM, Goto K, Kim DW, et al. Efficacy of zenocutuzumab in NRG1 fusion-positive cancer. N Engl J Med. 2025;392(6):566-576. doi:10.1056/NEJMoa2405008

For FULL References List, visit https://www.gotoper.com/annual-oncology-meeting-25-nrg1-postref

CME Posttest Questions

1 A patient is referred to you with a new diagnosis of metastatic
pancreatic ductal adenocarcinoma (PDAC) with multiple liver
metastases. The patient is asymptomatic and has an ECOG perform-
ance status of 0. Which of the following would be the next best step?

A. Germline testing for inheritable pathogenic mutations

B. Germline testing and somatic tissue testing

C. Somatic tissue testing only

D. Initiate systemic treatment without further testing

2 Blockade of which of the following molecules is an active
treatment approach in tumors with NRG1 fusions?

A. EGFR

B. HER3

C. HER4

D. NRG1

3 A patient with metastatic PDAC is referred to you after disease
progression on FOLFIRINOX. No somatic testing was performed at the time of diagnosis. On further investigation, the tumor has no evidence
of KRAS mutations but has an ATP1B1-NRG1 fusion. Which of the following therapies would you choose at this time?

A. Gemcitabine plus nab-paclitaxel

B. Zenocutuzumab

C. Zenocutuzumab plus gemcitabine

D. Clinical trial of an NRG1 antibody

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July 2, 2025
The NEID Earth Twin Survey. III. Survey Performance After Three Years on Sky

Time series of relative FWHM measurements for all NETS stars with multiple nights of data collected prior to August 2021. We observe a sharp decrease in FWHM in August 2021 for all Solar-type stars, and we interpret this as a break in the RV time series necessitating the definition of a new NEID RV era prior to this date. A sharp FWHM change is also observed for HD 95735, an M-dwarf, but this change does not follow that of the other stars, suggesting a chromatic dependence. Though the ∆FWHM time series for HD 170657 and HD 201091 stand out from the other Solartype stars, these variations reflect changing stellar activity levels rather than an instrumental effect. — astro-ph.EP

The NEID Earth Twin Survey (NETS) has been delivering a rich set of precise radial velocity (RV) measurements for 41 bright, nearby main sequence stars.

Here, we describe the status of the survey after three years on sky and we present the full set of RV measurements and accompanying stellar activity indicators. We discuss intermediate survey diagnostics, including calibration of the known RV zero point offset introduced following the Contreras fire in 2022 and the identification of an undiagnosed and previously unknown zero point offset in 2021.

An analysis of our data set using RVSearch demonstrates that for these target stars, NEID is independently sensitive to nearly all known planets with periods shorter than the NETS observing baseline. We also highlight a number of newly detected RV signals, which present exciting opportunities for future investigations.

Arvind F. Gupta, Evan Fitzmaurice, Suvrath Mahadevan, Paul Robertson, Jacob K. Luhn, Jason T. Wright, Sarah E. Logsdon, Daniel M. Krolikowski, Leonardo A. Paredes, Chad F. Bender, Mark R. Giovinazzi, Andrea S. Lin, Cullen H. Blake, Caleb I. Cañas, Eric B. Ford, Samuel P. Halverson, Shubham Kanodia, Michael W. McElwain, Joe P. Ninan, Jayadev Rajagopal, Arpita Roy, Christian Schwab, Guðmundur Stefánsson, Ryan C. Terrien

Comments: Submitted to the Astronomical Journal. 27 Pages, 12 Figures (including 5 Figure sets which are included in the source files)
Subjects: Earth and Planetary Astrophysics (astro-ph.EP); Solar and Stellar Astrophysics (astro-ph.SR)
Cite as: arXiv:2506.23704 [astro-ph.EP](or arXiv:2506.23704v1 [astro-ph.EP] for this version)
https://doi.org/10.48550/arXiv.2506.23704
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Submission history
From: Arvind Gupta
[v1] Mon, 30 Jun 2025 10:27:04 UTC (14,846 KB)
https://arxiv.org/abs/2506.23704
Astrobiology,

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July 2, 2025