ASCO GI Reaction
January 22, 2023

ASCO GI Reaction - SPOTLIGHT

ASCO GI Reaction
January 22, 2023

ASCO GI Reaction - SPOTLIGHT

Author

Zolbetuximab+ mFOLFOX6 as first-line treatment for patients with claudin-18.2+ / HER2−locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: Primary results from phase 3 SPOTLIGHT study

Abstract #LBA292: Kohei Shitara presented primary results of the P3 SPOTLIGHT trial assessing zolbetuximab + mFOLFOX6 vs placebo + mFOLFOX6 as first-line treatment in 565 previously untreated patients with CLDN18.2+ / HER2−locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma.

Results:

  • Zolbetuximab + mFOLFOX6 showed statistically significant improvement vs placebo + mFOLFOX6 in:
    • Median PFS: 61 vs 8.67 months
    • Median OS: 23 vs 15.54 months
  • ORR was similar between arms
  • Safety profile of zolbetuximab + mFOLFOX6 vs placebo + mFOLFOX6 was consistent with prior studies:
    • Most common TEAEs: nausea (82.4% vs 60.8%), vomiting (67.4% vs 35.6%), and decreased appetite (47.0% vs 33.5%)
    • Grade ≥3 TEAEs: 86.7% vs. 77.7%
    • Serious TEAEs were similar between arms (44.8% vs 43.5%)
    • TEAEs leading to discontinuations: 13.6% vs. 2.2%

Thought leader reactions were positive, with many oncologists opining that the superior PFS and OS results demonstrated by zolbetuximab + mFOLFOX6 means that the combination could become standard of care in this population.

Experts were also intrigued by how well the control group performed relative to expectations for FOLFOX6.

Some commentators mentioned that the next step in deciding SOC for this population would be comparing zolbetuximab vs immunotherapies, with one oncologist believing that nivolumab may offer better results in some cases.

Several oncologists noted that, with 38% of screened patients showing CLDN18.2 expression, CLDN18.2 should be added to the standard biomarker testing panel for mG/GEJ cancers.

A few thought leaders tempered their enthusiasm for the SPOTLIGHT results based on the increased GI toxicity (16% G3/4 vomiting w/zolbetuximab).

Summary:

Thought leaders believe that the PFS and OS data presented for zolbetuximab plus mFOLFOX6 are sufficient to potentially become new standard of care for CLDN18.2+HER2− mG/GEJ adenocarcinoma, though it has not been established that zolbetuximab is superior to immunotherapies and a few expressed concern about GI toxicities. Several commentators recommended adding CLDN18.2 to the standard biomarker panel for this cancer.

Expert synthesis powered by Opus Strategy LLC

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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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