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  • Mamdani’s New York victory exposes fault lines in Jewish Democratic politics – Reuters

    1. Mamdani’s New York victory exposes fault lines in Jewish Democratic politics  Reuters
    2. The bipartisan comfort with Islamophobia harms us all  Al Jazeera
    3. Mamdani’s victory has implications beyond America  Dawn
    4. Meet Mira Nair, Zohran Mamdani’s…

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  • Frontline STK-012 Plus Pembrolizumab and Chemo Shows Early Promise in PD-L1–Negative NSCLC

    Frontline STK-012 Plus Pembrolizumab and Chemo Shows Early Promise in PD-L1–Negative NSCLC

    The combination of STK-012 and standard-of-care pembrolizumab (Keytruda) plus chemotherapy (PCT) demonstrated early efficacy and safety when used as first-line treatment in patients with PD-L1–negative nonsquamous non–small cell lung cancer (NSCLC), according to data from the phase 1a/1b STK-012-101 trial (NCT05098132) presented during the 2025 SITC Annual Meeting.1

    No dose-limiting toxicities were reported, and most treatment-related adverse effects (TRAEs) were noted to be manageable and reversible. One grade 4 TRAE in the form of neutropenia was reported, and no grade 5 toxicities occurred. Notably, no TRAEs resulted in treatment discontinuation, and there were no substantive hallmark interleukin-2 (IL-2) TRAEs.

    At a median follow-up of 4 months (range, 1.3-12.2), the regimen elicited an objective response rate (ORR) of 55% in all efficacy-evaluable patients (n = 22), which was comprised entirely of partial responses (PRs); the disease control rate (DCR) was 96%. In those with a PD-L1 tumor proportion score (TPS) below 1% (n = 18) experienced an ORR of 50%, again comprised entirely of PRs, with a DCR of 94%.

    Top Takeaways Regarding STK-012 Combination in PD-L1–Negative NSCLC

    • STK-012 plus pembrolizumab and chemotherapy achieved an 55% response rate and a disease control rate of 96% in patients with PD-L1–negative nonsquamous NSCLC.
    • Responses deepened over time, including in patients with STK11 and KEAP1 mutations, with most remaining on treatment at cutoff.
    • The regimen showed manageable, reversible toxicity and no hallmark IL-2–related adverse effects, supporting further evaluation in phase 2.

    Moreover, those who received the combination of STK-102 and PCT experienced deepening of response over time; 15 of 22 patients were still receiving treatment at the time of the efficacy clinical cutoff date of September 15, 2025. In those with at least 1 immuno-oncology resistance TSG mutation (n = 11), the ORR with the combination was 55%; in those with 2 TSG mutations in the form of STK11 and KEAP1 (n = 4), this rate was even higher, at 75%.

    “Despite advances that have improved outcomes for newly diagnosed lung cancer patients, a significant unmet need persists—most notably among PD-L1–negative nonsquamous NSCLC and tumors with immune resistance mutations,” Adam J. Schoenfeld, MD, of Memorial Sloan Kettering Cancer Center, in New York, NY, stated in a news release.2 “Early STK-012 + SoC PCT data in these hard-to-treat populations are encouraging; if replicated in larger cohorts, they could reshape the treatment landscape.”

    What Was the Study Design of STK-012-101?

    The phase 1a portion sought to enroll 6 to 10 patients with stage IV nonsquamous NSCLC who were treatment naive, not selected for PD-L1 expression, and who did not have actionable genetic alterations.1 The phase 1b portion sought to include 20 to 40 patients with stage IV nonsquamous NSCLC who were treatment naive, without actionable genetic alterations, and who had a PD-L1 TPS below 1%.

    STK-012 was given in the outpatient setting at 2.25 mg subcutaneously for cycles 1 to 5+, pembrolizumab at 200 mg intravenously for cycles 1 to 5+, pemetrexed at 500 mg/m2 for cycles 1 to 5+, and carboplatin at area under the curve 5 for cycles 1 to 4. The primary end point was safety, and the secondary end point was ORR.

    In the efficacy-evaluable patients (n = 22), the median age was 69 years (range, 30-82), and 55% were male. Regarding ECOG performance status, 59% had a status of 0, and 41% had a status of 1. In terms of smoking status, 73% of patients were current or former smokers, and 27% had never smoked. With regard to PD-L1 TPS, the majority of patients (82%) had a TPS under 1% and 18% had a TPS of 1%. Most patients had non-mucinous adenocarcinoma (77%).

    At baseline, of the 11 patients with at least 1 TSG, 10 had STK11 mutations, 4 had KEAP1 mutations, and 2 had SMARCA4 mutations. Of the 4 patients with at least 2 TSG, 3 had STK11 and KEAP1, and 1 had STK11 with KEAP1 and SMARCA4. Eight patients had the following KRAS mutations: G12D (n = 3), G12V (n = 2), G13D (n = 1), G12C (n = 1), and Q61H (n = 1); 4 had KRAS mutation co-occurring with STK11.

    What Was the Safety Profile of STK-012 Plus Pembrolizumab and Chemotherapy?

    STK-012 plus PCT had a manageable toxicity profile. The safety clinical cutoff date was August 8, 2025. At a median follow-up of 3.12 months (range, 0.1-11.0), 25 patients were evaluable for safety; 10 of these patients were enrolled in the phase 1a portion of the research, and 15 were enrolled in the phase 1b portion. Grade 1/2 TRAEs occurred in 52% of patients; they were grade 3 or 4 for 28% of patients.

    The most common TRAEs reported in at least 10% of patients were nausea (grade 1/2, 44%), fatigue (grade 1/2, 36%; grade 3, 4%), rash/dermatitis (grade 1/2, 24%; grade 3, 16%), injection site reaction (grade 1/2, 28%), diarrhea (grade 1/2, 28%), pyrexia (grade 1/2, 16%), anemia (grade 1/2, 4%; grade 3, 12%), decreased appetite (grade 1/2, 16%), neutropenia (grade 3, 8%; grade 4, 4%), chills (grade 1/2, 12%), cough (grade 1/2, 12%), and vomiting (grade 1/2, 12%).

    No significant IL-2 TRAEs were reported. Eight percent of patients each experienced grade 1/2 increase in aspartate and alanine aminotransferase, and 4% of patients experienced lymphopenia.

    What’s Next for STK-012?

    The phase 2 portion, SYNERGY-101, is recruiting patients with nonsquamous NSCLC who have stage IIIB/IIIC or IV disease and who are treatment naive.3 Patients will be required to have a PD-L1 TPS below 1% per local testing and test negative for actionable genetic alterations.

    Patients (n = 105) will be randomized 1:1:1 to receive STK-012 at 2.25 mg with PTC every 3 weeks or STK-012 at 1.5 mg plus PTC every 3 weeks, or PTC alone. Stratification factors comprise ECOG performance status (0 vs 1) and smoking status (current vs former). The primary end point is ORR by blinded independent central review.

    References

    1. Schoenfeld AJ, Garon EB, Chiang AC, et al. Initial phase 1a/1b results of STK-012, an α/β IL-2 receptor biased partial agonist, with pembrolizumab, pemetrexed, and carboplatin in 1L PD-L1 negative non-squamous NSCLC. Presented at: 2025 SITC Annual Meeting; November 5-9, 2025; National Harbor, MD. Accessed November 8, 2025.
    2. Synthekine presents positive initial results from phase 1a/1b clinical trial of STK-012 plus pembrolizumab and chemotherapy in first-line, PD-L1 negative nonsquamous non-small cell lung cancer. News release. Synthekine, Inc. November 7, 2025. Accessed November 8, 2025. https://www.businesswire.com/news/home/20251107945337/en/Synthekine-Presents-Positive-Initial-Results-from-Phase-1a1b-Clinical-Trial-of-STK-012-Plus-Pembrolizumab-and-Chemotherapy-in-First-Line-PD-L1-Negative-Nonsquamous-Non-Small-Cell-Lung-Cancer
    3. STK-012 monotherapy and in combination therapy in patients with solid tumors. ClinicalTrials.gov. Updated August 7, 2025. Accessed November 8, 2025. https://clinicaltrials.gov/study/NCT05098132

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  • Significant Demographic Headwinds in China

    Significant Demographic Headwinds in China

    In 1963, 33 million babies were born in China. In 2024, there were 9 million, see chart below.

    Sources: United Nations, Apollo Chief Economist

    Download high-res chart

    This presentation may not be distributed, transmitted or otherwise communicated to others in whole or in part without the express consent of Apollo Global Management, Inc. (together with its subsidiaries, “Apollo”).  

    Apollo makes no representation or warranty, expressed or implied, with respect to the accuracy, reasonableness, or completeness of any of the statements made during this presentation, including, but not limited to, statements obtained from third parties. Opinions, estimates and projections constitute the current judgment of the speaker as of the date indicated. They do not necessarily reflect the views and opinions of Apollo and are subject to change at any time without notice. Apollo does not have any responsibility to update this presentation to account for such changes. There can be no assurance that any trends discussed during this presentation will continue.   

    Statements made throughout this presentation are not intended to provide, and should not be relied upon for, accounting, legal or tax advice and do not constitute an investment recommendation or investment advice. Investors should make an independent investigation of the information discussed during this presentation, including consulting their tax, legal, accounting or other advisors about such information. Apollo does not act for you and is not responsible for providing you with the protections afforded to its clients. This presentation does not constitute an offer to sell, or the solicitation of an offer to buy, any security, product or service, including interest in any investment product or fund or account managed or advised by Apollo. 

    Certain statements made throughout this presentation may be “forward-looking” in nature. Due to various risks and uncertainties, actual events or results may differ materially from those reflected or contemplated in such forward-looking information. As such, undue reliance should not be placed on such statements. Forward-looking statements may be identified by the use of terminology including, but not limited to, “may”, “will”, “should”, “expect”, “anticipate”, “target”, “project”, “estimate”, “intend”, “continue” or “believe” or the negatives thereof or other variations thereon or comparable terminology.


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  • One missing feature stops me from switching to Samsung Internet

    One missing feature stops me from switching to Samsung Internet

    Hadlee Simons / Android Authority

    Chrome has been my default browser for a long time, but recently I’ve been looking into alternatives that offer useful new features that Google’s browser can’t match. There’s always one sticking point that…

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  • Beelink EQR6 is the most powerful computer under £300 in the UK with a Ryzen 7 6800U processor, 24GB RAM and 1TB SSD

    Beelink EQR6 is the most powerful computer under £300 in the UK with a Ryzen 7 6800U processor, 24GB RAM and 1TB SSD

    The best mini PCs have become a practical alternative to bulky desktops, offering serious power in a compact form. The Beelink EQR6 Mini PC pushes that idea further, packing high-end laptop performance into a palm-sized computer.

    With Black…

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  • Listening to Music Has a Surprising Impact on Dementia Risk, Study Shows : ScienceAlert

    Listening to Music Has a Surprising Impact on Dementia Risk, Study Shows : ScienceAlert

    Listening to music into old age could reduce the risk of dementia by almost 40 percent, a new study has found.

    It’s based on data from 10,893 Australians aged 70 or older, who, at the time of recruitment, were living in retirement communities…

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  • We’re Hiring! – by Leonora Barclay

    We’re Hiring! – by Leonora Barclay

    Come join our team!

    Persuasion is looking for a Director of Operations—a leader who is committed to liberal values and has the skills and experience to steer the organisation forward.

    Over the last five years, we’ve grown into a leading liberal…

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  • Dollar volatility tumbles as currency markets move past ‘Trump shock’

    Dollar volatility tumbles as currency markets move past ‘Trump shock’

    Unlock the White House Watch newsletter for free

    Currency markets have moved beyond the “Trump shock” that sparked big gyrations earlier in the year, as measures of dollar volatility tumble to levels last seen before the US presidential election.

    Expectations of swings in the dollar’s value against the euro and the yen, which spiked following Donald Trump’s election last November, have fallen this month to their lowest in more than a year, according to indices provided by CME Group.

    At the same time the US dollar index, which measures the greenback against a basket of currencies including the pound and the euro, has regained some of the year’s sharp losses to trade close to its level before it began to surge in the run-up to Trump’s win.

    Investors and analysts say a series of tariff deals with big US trading partners such as the EU and China have sucked volatility out of the market, while the US economy has weathered the onset of tariffs better than many expected. Meanwhile, big central banks are nearing the end of their cycle of interest rate cuts, draining another source of market instability.

    “The world is learning to live with Trump,” said Chris Turner, head of markets research at ING. “Investors have learned to deal with headlines with a pinch of salt.”

    The dollar strengthened before the US election on a bet — labelled the “Trump trade” — that the Republican’s trade and tax policies would strengthen the world’s biggest economy and its currency. 

    That unravelled dramatically as Trump’s tariff announcements in April rocked currency markets, with a record nearly $10tn in daily FX volumes that month. 

    Worries about the domestic economic impact of the trade war as well as concerns over Federal Reserve independence sent the dollar index tumbling to its worst start to the year since the 1970s.

    But the dollar has ground higher since the summer, helped by a rally in US stocks that carried Wall Street to record highs before this week’s pullback in tech shares. Some big fund managers argue worries over US assets were overdone. 

    “For all the talk of the end of US exceptionalism, when you look at the big picture, the dollar has been a strong currency for several years,” said Robert Tipp, head of global bonds at PGIM, suggesting that the dollar’s decline this year represents a “correction in a bull market” rather than “the beginning of the end”. 

    Line chart of ICE US Dollar index, points showing Dollar stabilises after sharp drop

    The collapse in volatility expectations is the market saying “the ‘Trump shock’ is over”, wrote Deutsche Bank’s George Saravelos in a note this week, pointing to easing trade tensions and fiscal policy on “autopilot”. 

    “What else is there for President Trump to do to shock the market? We are struggling to come up with an answer ourselves.”

    A lack of US macroeconomic data due to the country’s longest-ever government shutdown has also dulled volatility in the dollar and US Treasury markets, analysts say.

    Investors with limited comprehensive data information about inflation, the labour market and consumer spending have held off from taking big positions. A measure of volatility in the Treasury market — ICE’s Move Index — has fallen to four-year lows since the shutdown began.

    The dollar has also received a boost from last month’s Federal Reserve meeting, where the central bank cut rates but warned that the next cut was not a “foregone conclusion”. A slower pace of rate cuts would typically support the currency.

    Investors said this showed the currency was now responding to the traditional determinants of currency strength, principally differences in interest rates between countries. “We’ve settled back into more traditional drivers of FX,” said ING’s Turner.

    Demand for call options on the dollar, a bet that the currency will strengthen, is outpacing put options by the most since February, according to separate data from CME Group.

    Some fund managers said the dollar was regaining its traditional role as a stabiliser in their portfolios, because of its tendency to strengthen in times of global stress: a quality that had been called into question when the currency plunged alongside risky assets following Trump’s April tariff salvo.

    The start of the year was “more of an anomaly than the trend”, said Rushabh Amin, a portfolio manager at Allspring Global Investments. “We think the dollar will continue to act as a portfolio diversifier going forward, particularly for foreign investors.”

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  • EU climate rules risk energy security, warn gas suppliers – Financial Times

    EU climate rules risk energy security, warn gas suppliers – Financial Times

    1. EU climate rules risk energy security, warn gas suppliers  Financial Times
    2. ExxonMobil Threatens To Leave EU Over Sustainability Rules  Crude Oil Prices Today | OilPrice.com
    3. Europe’s green rules stir row, draws international flak: India opposes, Qatar warns  Firstpost
    4. Exclusive-QatarEnergy, Exxon Executives Warn of Europe Exit Over Climate Law  US News Money
    5. Darren Woods Warns EU: Soften Rules or Exxon Exits Europe  Business Chief

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  • Unprecedented radio view of the Milky Way took over 40,000 hours to construct — Space photo of the week

    Unprecedented radio view of the Milky Way took over 40,000 hours to construct — Space photo of the week

    Quick facts

    What it is: The Southern Hemisphere view of the Milky Way galaxy

    Where it is: All around us

    When it was shared: Oct. 29, 2025

    We cannot see or image the entire Milky Way galaxy, because we are located inside it. From Earth, we can…

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