Sandy Algaze

GI Medical Oncologist @USC Norris | Clinical investigator | GI cancers | Coffee, beaches & big ideas ☕🌊

[Nicholas Hornstein @GIMedOnc]

And just like that, adagrasib + cetuximab is no longer FDA approved for KRAS G12C colorectal cancer.

The accelerated approval was officially withdrawn September 1 after KRYSTAL-10 failed to confirm benefit.

We talked about KRYSTAL-10 when it was presented earlier this year.

The phase III randomized 461 patients in 2L to adagrasib + cetuximab vs chemotherapy �� VEGF inhibition.
It missed both primary endpoints:
▪️PFS: 7.5 vs 8.1 months, HR 0.89
▪️OS: 21.6 vs 21.7 months, HR 0.83

Hard to argue with a negative phase III trial.

But I still like the idea of a chemo free option.

Response rate was 47% vs 16%.
That could matter for some patients (like those who you need just a little more shrinkage to enable crative intent therapy).

KRYSTAL-10 asked whether adagrasib + cetuximab was better than chemotherapy in 2L.

It wasn’t.

That doesn’t mean the concept of KRAS G12C + EGFR blockade was wrong. And it doesn’t mean there aren’t patients for which this isnt valuable.

Anyone celebrating this should look themselves in the mirror; this is a tool that has just been removed from our arsenal. However, the FDA did exactly what the system is designed to do; pull back if the Ph III doesnt pan out after accelerated approval.

@OncoAlert @TheGutOncLab @Onco_Nexus

[Sandy Algaze @AlgazeMD]

@jgong15 @FDA @NatureCancer @OncoAlert @MOASC_Office @montypal @CParkMD @crisbergerot @PauloBergerot @imedverse @VJOncology @NazliDizman @ronanhsieh @MedNewsWeek Congratulations!

[Jun Gong, MD @jgong15]

1/🧵

IITs/ISTs are often a labor of love. Proud to share that our phase I GlutaPanc trial testing the feasibility of pairing @FDA approved high-dose L-glutamine (L-Gln) + #1L gem/nab-paclitaxel (GA) in #mPDAC was published in @NatureCancer

https://t.co/xgi40gjbqP

@OncoAlert

[Pashtoon Kasi MD, MS @pashtoonkasi]

🆕👇🏽Unveiling FULL results of our #NEST🪺 Trial in MSS “cold”🧊colorectal cancer

💡Immunotherapy (BOT🤖/BAL) BEFORE surgery
💯% disease-free to date✅
NEST1:~32 months
NEST2:~24 months

5 years of work—now in @CCR_AACR🙌🏽

🚀#NEST3 NOW OPEN!

@OncoAlert
🔗 https://t.co/jeRklgce1c

[Jun Gong, MD @jgong15]

❓@GIcancerDoc @GIMedOnc @IbrahimSahinMD1 @ronanhsieh @guildsman @CathyEngMD @Salthecancerguy @DanZhaoMD @OncoAlert as the label is written, in a pt fit for multi-agent chemo would you ➡️ to daraxonrasib or ➡️ w/chemo #1L? Imagine co-pay and drug will be costly w/payor pushback

[Nicholas Hornstein @GIMedOnc]

🚨 This may be the most consequential oncology study of 2026.

Yes, on par with daraxonrasib.

At #ASCO26 we highlighted the 5-year KEYNOTE-942 data for the individualized mRNA cancer vaccine intismeran + pembrolizumab in resected high-risk melanoma.

And the numbers were 👀

RFS HR 0.51
5-year RFS: 68.8% vs 49.1%
DMFS HR 0.41
OS HR 0.47 (still immature)

Amazing data. But 157 patients. Phase IIb.

The big question: does it hold up in phase III?

Apparently, yes. 🔥

INTerpath-001 randomized 1,137 patients with resected stage IIB-IV melanoma to intismeran + pembrolizumab vs pembrolizumab alone.

At the prespecified interim analysis:

✅ RFS met
✅ DMFS met
✅ Statistically significant AND
✅ No new safety signals

We don’t have the HRs yet. So some restraint until we see the actual data (also this is a press release, so grain of salt)

But why is this such a big deal?

Because this isn’t really about melanoma.

🧬 Sequence YOUR tumor
🎯 Identify YOUR neoantigens
💉 Manufacture a vaccine specifically for YOUR cancer
🦠 Train YOUR immune system to recognize it

And now that approach has succeeded in a randomized phase III trial.

This is actually personalized.

And if this platform works across tumor types, the implications are enormous.

Daraxonrasib may change how we treat RAS-driven cancers.

INTerpath-001 may change how we think about cancer vaccines altogether.

2026 has been an amazing year for oncology advances. 🔥

https://t.co/ePz5O6P1rT

@OncoAlert @Onco_Nexus @TheGutOncLab

[Sherene Loi, MD @LoiSher]

🚩Can an mRNA vaccine make “cold” tumours more responsive to immunotherapy 🌶️?

A recent @Nature study suggests mRNA vaccination may activate systemic innate immunity & potentially sensitise tumours to checkpoint blockade.

The clinical data need prospective validation, but the biological concept is compelling.

The Authors discuss the implications in an @esmo_iotech commentary. 🙏@adam_grippin @StevenLin_MDPhD

Nature article linked: https://t.co/BE5zV4EEDm
IOTECH commentary: https://t.co/wmplUX63yk

@myESMO @esmo_iotech #CancerImmunotherapy #mRNA #ImmunoOncology #ESMO #ESMOIOTECH

[Dr. Nina Niu Sanford @NiuSanford]

BEACON-HCC is a MultiD treatment allocation framework for HCC reflecting contemporary practice, w explicit incorporation of SBRT & Y90 based on current evidence.

It's outstanding, timely & what I plan to use in practice.

👏👏👏 @OncoAlert

[USC Norris Comprehensive Cancer Center @uscnorris]

110 community health workers trained on colorectal cancer prevention, a joint effort by @uscnorris, @USCCOPECC, @Genentech & @CaRE2HEC.

Storytelling + education = healthier communities.

[GI Oncology Now @GiOncNow]

❗️ In case you missed it: The FDA has approved the use of SimpleScreen, a blood-based test developed by Freenome for the detection of #colorectalcancer, based on positive results from the PREEMPT CRC study. https://t.co/lQEcXdMT4b

[Ibrahim Halil SAHIN, MD @IbrahimSahinMD1]

✳️ It was wonderful to meet with colleagues in San Diego and discuss the evolving landscape of colorectal cancer across all stages, including the latest updates and what the future holds, at the #BackTable Tumor Board last Saturday❗️It was truly stimulating discussion with several key points❗️

✳️ It was also a pleasure to reconnect with longtime colleagues, meet new friends in the field, and spend time with the outstanding BackTable team. Looking forward to next year❗️

@jgong15 @_backtableONC @AlgazeMD @AGangiMD @AaronFrittsMD

[Jun Gong, MD @jgong15]

A fantastic production by @_backtableONC @AaronFrittsMD‼️can’t wait to see the episodes, thx for hosting a #GIonc dream team indeed @AlgazeMD @IbrahimSahinMD1 @AGangiMD @ronanhsieh @DaniCastilloMD @geoffreybuckle @Ahn_Daniel_Onc @AdamYopp @DrArsenOsipov @DrHendifar @Kate_Baker_MD

[Jun Gong, MD @jgong15]

‼️PhIII #ctDNA-guided vs standard CT surveillance in resected #CRC ➡️ ctDNA-guided group sig ⬆️ rate of curative-intent treatment (48.1% v 23.6%, RR 2.03, P=0.008), Longer F/U needed for RFS/OS endpoints

@OncoAlert @IbrahimSahinMD1 @ronanhsieh @manjuggm

https://t.co/YVrsRtasWR

[Nieves Martinez Lago MD PhD @DraMartinezLago]

🧬 MSS colorectal cancer

🎯 Precision oncology beyond RAS/RAF

💊 ADCs & bispecifics
🛡️ TME-targeted strategies
🧬 CAR-T and DDR approaches
🤖 Spatial profiling + AI

🔗 https://t.co/fXwR8KZ6en

@OncoAlert

[Sandy Algaze @AlgazeMD]

Excited to share our review on next-generation precision oncology in MSS colorectal cancer. Grateful to collaborate with Michela Bartolini and for the mentorship of Heinz-Josef Lenz.

https://t.co/MFfpfAzGAz

#ColorectalCancer #PrecisionOncology #OncTwitter

[BackTable Tumor Board @_backtableONC]

Last week's GI Oncology Creator Weekend brought together an incredible group of physicians for nine recording sessions — so much great content headed your way. Huge THANK YOU to all of our contributors and to @jgong15 for putting together an absolute dream team!

@IbrahimSahinMD1 @AGangiMD @AlgazeMD @Kate_Baker_MD @DaniCastilloMD @ronanhsieh @DrArsenOsipov @geoffreybuckle @DrHendifar @AdamYopp @the_danielahn

Download the BackTable app now so you're first in line when these episodes drop.

https://t.co/WFLNztosXJ

#GIOnc #Oncology #MedTwitter #TumorBoard

[BackTable Tumor Board @_backtableONC]

Session FIVE is underway! @jgong15 is joined by Dr. Sandra Algaze and @IbrahimSahinMD1 to discuss molecular-driven therapies in CRC. All-Star line up!

@CedarsSinai @UMich @KeckMedicineUSC #CancerCare #GIoncology @Kate_Baker_MD @DaniCastilloMD @ronanhsieh