David S. Hong MD retweeted
With many new cancer medicines, reminder that
the clinical effectiveness of drug combinations is highly predictable from the clinical effectiveness of single agents
100% sensitive prediction of phase 3 trial success across all advanced cancers, 1995-2020
nature.com/articles/s4301…
the clinical effectiveness of drug combinations is highly predictable from the clinical effectiveness of single agents
100% sensitive prediction of phase 3 trial success across all advanced cancers, 1995-2020
nature.com/articles/s4301…
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David S. Hong MD retweeted
Despite staggering advances in basic science, drug development research is only getting slower. The main culprit? Increasing clinical trial timelines. The median clinical development pathway has increased from 8.4 years to 9.3 years and pipeline creation has slowed 32% even as
This is the point I keep making about the main bottleneck to drug discovery and why AI on its own won't be enough. These timelines aren't going anywhere (ofc AI can be used creatively to ease such bottlenecks -- eg via better endpoints that allow smaller cohorts for trials, followed up for shorter periods of time).
This is the point I keep making about the main bottleneck to drug discovery and why AI on its own won't be enough. These timelines aren't going anywhere (ofc AI can be used creatively to ease such bottlenecks -- eg via better endpoints that allow smaller cohorts for trials, followed up for shorter periods of time).
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The Maestro of Drug devlopment! @kevansf
Kevan Shokat (@kevansf), a professor of cellular and molecular pharmacology at UC San Francisco (@UCSFCancer), has won the second annual Stephenson Global Prize for research in pancreatic cancer.
cancerletter.com/conversation-w…
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History never repeats but it rhymes!
GenFleet's October 2026 investor presentation reports clinical activity with the chemotherapy-free combination of GFH375 (KRAS G12D inhibitor) and cetuximab (EGFR antibody) in metastatic colorectal and pancreatic cancers, following earlier acceptance for full ESMO 2026 submission.
Heavily pretreated mCRC (n=54):
- ORR: 44%
- DCR: 89%
- Median PFS: 7.3 months (median follow-up 5.4 months)
- 94% treated in third line or later
- 50% treated in fourth line or later
- 65% remained on treatment at data cutoff
First-line KRAS G12D-mutant PDAC (n=24):
- ORR: 71%
- DCR: 100%
- 88% remained on treatment
- 96% had metastatic disease
- Median follow-up: 3.8 months, with only three PFS events
What cetuximab may add, monotherapy vs combination:
Metastatic CRC (both previously treated):
- ORR: 11% → 44%
- DCR: 71% → 89%
- Monotherapy n=28; combination n=54
PDAC (different treatment settings):
- ORR: 40.7% → 71%
- DCR: 96.7% → 100%
- Monotherapy n=59 (previously treated); combination n=24 (first-line)
The contribution of cetuximab is particularly interesting in CRC, where the combination's higher response rate may reflect suppression of adaptive EGFR signaling. In PDAC, differences in treatment line limit direct comparison. These are nonrandomized cohorts.
Tolerability (n=78):
- Grade 3 treatment-related adverse events: 24%
- Treatment interruptions: 21%
- Dose reductions: 5%
- Treatment-related discontinuations: 0%
- No Grade 4–5 treatment-related adverse events
GI events were frequent, predominantly low-grade, with limited information on their evolution over successive treatment cycles.
US experience with VS-7375 🇺🇸(the same molecule as GFH375 🇨🇳): GI adverse events are predominantly front-loaded, attenuating after the first cycle. Administration with food and prophylactic antiemetics have improved tolerability. An improved formulation is under development, with no vomiting observed in preliminary canine testing, aiming to further improve tolerability without compromising antitumor activity.
Why chemotherapy-free treatment matters: real-world attrition and patient choice.
Metastatic CRC, Danish nationwide registry (n=7,202):
- 46.4% never initiated first-line systemic treatment
- 47.6% of treated patients reached second line
- 20.3% of treated patients reached third line
Metastatic PDAC, 2026 US real-world analysis (n=2,708):
- 35% received no systemic therapy
- 52% of patients starting chemotherapy discontinued within 90 days
- 34% of chemotherapy starters discontinued within 90 days without documented disease progression
Metastatic PDAC, Netherlands nationwide study (n=13,756):
- 72% received no systemic therapy
- Patient or family preference accounted for 39% of reported reasons for withholding systemic treatment
Daraxonrasib Phase III, RASolute 302:
- 15.1% randomized to chemotherapy never initiated treatment
- 2.8% randomized to daraxonrasib never initiated treatment
The burden of chemotherapy is real. Patients can tolerate only so much treatment, and its physical and personal costs can limit what remains possible. The potential of chemotherapy-free regimens extends beyond avoiding cytotoxic therapy: durable disease control while preserving patient fitness, treatment continuity and future therapeutic options.
@FAndreMD @EileenMOReilly
@Aiims1742 @MPishvaian
#KRAS #G12D #GFH375 #PDAC #ESMO26
📎
genfleet.com/Public/Uploads…
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David S. Hong MD retweeted
@ANaingMD et al. presents a position paper titled "The immune checkpoint inhibitors journey: From early promise to lasting impact" doi.org/10.36401/JIPO-… #AI #AIhealthcare #immunecheckpointinhibitors #ICIs #cancercare #cancerresearch
@HajjarJoud
@BettzyStephen
@ajaysheshadri
ewantiLimaye
@jibranahmed1
@weoncologists
@MDerbalaMD
@mirella_nardo
@ErulEnes
@ImeneHadji1
@RegmiSunil1
@HajjarJoud
@BettzyStephen
@ajaysheshadri
ewantiLimaye
@jibranahmed1
@weoncologists
@MDerbalaMD
@mirella_nardo
@ErulEnes
@ImeneHadji1
@RegmiSunil1
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Come Join the party!!!
Join this amazing community during the era of the RAS Revolution (@DavidHongMD docet)! Do your part at advancing RAS targeting and its clinical impact. We are looking for outstanding findings and clinical trials to be selected for oral presentations😊 submit an abstract by 11/2
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The man, the myth!
Young-onset colorectal cancer is rising, and CRC demands focus. @MDAndersonnews has created a dedicated Department of Colorectal Medical Oncology to meet that challenge. Honored to serve as its inaugural Chair and partner with new GI Med Onc chair Arvind Dasari @adasarimd #CRCSM
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Final day at the NCI RAS Summit! What amazing summit! RAS is like an onion when you think know everything-there is another layer to peel! @NCIDirector @UTMDAnderson
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Day #2 of the NCI RAS Summit. A tradition highlight-Korean BBQ with RAS crew! We missed you Frank, Kevan, Tyler and Dave!@UTMDAnderson
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Day#2 of the RAS NCI meeting! Still
More amazing science and more Amazing people!@UTMDAnderson
More amazing science and more Amazing people!@UTMDAnderson
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Superstar! Dr Wung Ki Hong would be proud!
Some honors🏅mean more than words can express. 💙
I was deeply honored to deliver the Waun Ki Hong Memorial Lecture at the Severance Alumni Association Annual Meeting.
Dr. Waun Ki Hong was a true pioneer in oncology and physician-scientist leadership. Someone I have admired for otsteps I have aspired to follow.
This was particularly meaningful because Dr. Dong M. Shin, another remarkable pioneer and my mentor, delivered this lecture last year.
Standing there and reflecting on their extraordinary contributions to cancer medicine was both humbling and deeply emotional.
I am reminded that our journeys are shaped by those who came before us. Their mentorship, vision and courage give the next generation the confidence to pursue what once seemed impossible.
This experience reminded me to dream bigger, aim higher and remain committed to making a meaningful difference for our patients.
Deeply grateful to the Severance alumni community, my mentors and everyone who has been part of this journey.
The best way to honor those who paved the way is to keep moving forward. 💜
#WaunKiHong #Severance #Yonsei #PhysicianScientist #CancerResearch #Mentorship #Oncology @yonsei_u @yonseicancer
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