ESMO IO '22 reaction
December 14, 2022

ESMO-IO Reaction - KRYSTAL-7 and KRYSTAL-1

ESMO IO '22 reaction
December 14, 2022

ESMO-IO Reaction - KRYSTAL-7 and KRYSTAL-1

Author

Abstract # LBA4: Pasi Jänne presented preliminary efficacy and safety results of adagrasib in combo with pembrolizumab in 82 treatment-naïve patients with advanced NSCLC harboring a KRASG12C mutation enrolled in the P2 KRYSTAL-7 (n=75) trial and the P1b cohort of the KRYSTAL-1 (n=7) trial.

Results:

  • Krystal-7 (n=75):
    • ORR: 49% (56% in pts enrolled ≥6 months)
    • DCR: 89%
    • Responses observed in 59% of pts with PD-L1 TPS ≤50%; 48% with PD-L1 TPS 1-49%; and 30% with PD-L1 TPS <1%
    • DOR, PFS, and OS not mature
    • Grade 3-4 TRAEs occurred in 44% of pts; no Grade 5 TRAEs
    • Both ada and pembro discontinuation occurred in 3% of pts
  • KRYSTAL-1 (n=7):
    • ORR: 57%; DCR: 100%
    • Safety consistent with KRYSTAL-7

Thought leader reactions were cautiously optimistic. Several found the response rates of first-line ada + pembro promising, but noted that these are early results.

The toxicity profile was considered manageable, but there were concerns regarding early drop-outs and deaths.

Summary:

Thought leaders are optimistic about the early phase response rates and safety data of first line adagrasib + pembrolizumab in this population (1L NSCLC, KRASG12C mutation); however, more mature data is needed to gauge whether adagrasib has a place as a first line NSCLC treatment.

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Not rated
Allison Betof Warner, MD, PhD (she/her) 4
3743
Manhattan, NY
November 10, 2022

79% had reduction in disease. ORR 31%. Many responses deepen over time.

Not rated
Allison Betof Warner, MD, PhD (she/her) 3
3743
Manhattan, NY
November 10, 2022

Median DOR not yet reached. Median OS 13.9 mo. 12 mo OS was 54%. As typical with immunotherapy, we see a nice tail on the curve. #TIL#SITC22

Positive
Alex Shoushtari, MD
2253
New York, USA
November 10, 2022

Important work on efficacy of TIL therapy lifileucel in PD-1 resistant #melanoma being presented at #SITC22. Pretty good durability for this heavy lift of a treatment.

Not rated
Allison Betof Warner, MD, PhD (she/her) 2
3743
Manhattan, NY
November 10, 2022

Toxicity profile was in line with prior TIL/Lifileucel data. No surprises here. Median # doses of IL-2 was 6.

Positive
Hussein Tawbi, MD, PhD
1685
Houston, TX
November 10, 2022

Absolutely agree!… this should be available to our melanoma patients ASAP!… and paves the way for smarter cellular therapies to be designed, studied, and eventually widely disseminated

Positive
Allison Betof Warner, MD, PhD (she/her) 1
3744
Manhattan, NY
November 10, 2022

Where does this leave us with #TIL therapy for #melanoma? IMO, this response rate/durability justifies accelerated approval. Pts with PD-1 refractory melanoma need options. It’s FAR from a perfect tx but provides meaningful clinical benefit. What say you melanoma Twitterverse?

Not Rated
Sumanta K. Pal, MD, FASCO
15083 Followers
Los Angeles, CA
November 8, 2022

Just before I start AM clinic at @cityofhopeoc, excited to share results from #COBALT_RCC, a P1 trial of @CRISPRTX#CTX130 in #kidneycancer in the @sitcancer#PressProgram. Will present more on Thurs 5:37p at #SITC22! Thx @neerajaiims@DrBenTran@HaanenJohn#SamerSrour& co-Is! t.co/aDnhG9n92A

not rated
Shilpa Gupta
5095 Followers
Cleveland, OH
November 8, 2022
Not Rated
Tian Zhang, MD, MHS
6463 Followers
Dallas, TX
November 8, 2022

CAR-Ts are coming for #kidneycancer!! Congratulations @montypal and team; can’t wait to see results at #SITC22! t.co/9MrlF2yzBe

Not Rated
Moshe Ornstein MD
1930 Followers
Cleveland, OH
November 8, 2022

Congrats @montypal and team! Great to see CAR T therapy coming to #RCCt.co/ypRHBC89Pt

Not Rated
Shuchi Gulati MD
12476 Followers
Seattle, WA
November 8, 2022

Another huge step from none other than @montypal!! CAR-Ts in #kidneycancer!Congratulations to the entire team!Looking forward to seeing the results at #SITC22! t.co/HvKeVBPyV7

Not Rated
Petros Grivas
12476 Followers
Seattle, WA
November 8, 2022

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