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Goutham Sunny: Breakthroughs in Targeted Cancer Therapies

Goutham Sunny/X

Jun 7, 2025, 16:30

Goutham Sunny: Breakthroughs in Targeted Cancer Therapies

Goutham Sunny, Former Resident Doctor at The Gujarat Cancer and Research Institute, shared key highlights from recent breakthroughs in targeted cancer therapy on X:

“SAVANNAH Trial (Phase II) Update – EGFR-mutant NSCLC. MET-driven resistance after 1L osimertinib? A new oral combo shows promise!

Savolitinib + Osimertinib

MET IHC3+/≥90% and/or FISH10+ population

ORR: 56%

mDoR: 7.1–9.9 mo

mPFS: 7.4–7.5 mo

Well tolerated (edema, nausea, diarrhea most common)

Clinically meaningful, durable responses. Precision-matched to MET-amplified/overexpressed tumors. Chemotherapy-sparing targeted option

Limitations:

Benefit confined to high MET expressers

Resistance still emerges

Phase III (SAFFRON) data awaited for practice change

SAVANNAH highlights the growing role of biomarker-driven therapy to tackle osimertinib resistance in EGFR+ NSCLC!”

“Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study”

Authors: F. de Marinis, T.M. Kim, L. Bonanno, S. Cheng, S.-W. Kim, M. Tiseo, Q. Chu, C. Proto, A. Sacher, Y.-H. Luo, S. Novello, D. Hao, C. Baik, L. Bazhenova, J.S. Lee, B.C. Cho, J. Cadranel, T.B. Diep, G. Metro, P. Narayanan, Y. Yoneshima, J. de Castro Carpeño, C. Baldotto, C. Nyhus, J.C.-H. Yang, L.V. Sequist, B. Levy, R. Hartmaier, I. Igwegbe, L. Poole, W. Xu, M.-J. Ahn

Breakthrough in Targeting TP53 Mutations

“Major Breakthrough in Targeting TP53 Mutations! Rezatapopt (PC14586) reactivates the p53 Y220C mutant—a long-considered “undruggable” target in cancer.

Why it matters:

Restores wild-type p53 tumor suppressor function

Triggers antiproliferative effects in cancer cells

Shows potent single-agent and combo efficacy (incl. with immunotherapy)

Validated by deep structural and functional studies

Now in registrational Phase II trial for TP53 Y220C+ solid tumors

Significance: First-in-class agent with real potential to change the game for patients with p53-mutant cancers—a long-standing unmet need!”

“Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator”

Authors: Anna M. Puzio-Kuter, Lizhong Xu, Mary Kate McBrayer, Romyr Dominique, Hongju H. Li, Bruce J. Fahr, Alyssa M. Brown, Amy E. Wiebesiek, Brandon M. Russo, Chris L. Mulligan, Hong Yang, Josh Battaglia, Kimberly A. Robell, Dafydd H. Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D. Greenbaum, Jonathan D. Oliner, Thomas W. Davis, Melissa L. Dumble, Melissa L. Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M. Fellous, Binh T. Vu, Alison M. Schram, Arnold J. Levine, Masha V. Poyurovsky

Goutham Sunny: Breakthroughs in Targeted Cancer Therapies

Breakthrough in Solid Tumor CAR-T Therapy

“Breakthrough in Solid Tumor CAR-T Therapy!

Engineered scFvs precisely target mutant KRAS (G12V)

Neoantigen-specific CAR-Ts (NeoCARs) show strong in vitro and in vivo anti-tumor activity

Smart ‘armored’ NeoCARs with inducible IL-12 boost antigen presentation and cytotoxicity

TCR knockout – improved safety in vivo

Significance: Tackles the holy grail of solid tumors—KRAS-mutant cancers—offering a next-gen modular CAR-T platform with enhanced precision, efficacy, and safety for lung, pancreas, and RCC tumors.”

“Mutant KRAS peptide targeted CAR-T cells engineered for cancer therapy”

Authors: Alexander Benton, Jiageng Liu, Mathilde A. Poussin, Andrea Lang Goldgewicht, Madhara Udawela, Adham S. Bear, Nils Wellhausen, Beatriz M. Carreno, Pete M. Smith, Matthew D. Beasley, Ben R. Kiefel, Daniel J. Powell Jr.

Goutham Sunny: Breakthroughs in Targeted Cancer Therapies

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Insight

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Insight

Goutham Sunny: Breakthroughs in Targeted Cancer Therapies

Goutham Sunny, Former Resident Doctor at The Gujarat Cancer and Research Institute, shared key highlights from recent breakthroughs in targeted cancer therapy on X:

“SAVANNAH Trial (Phase II) Update – EGFR-mutant NSCLC. MET-driven resistance after 1L osimertinib? A new oral combo shows promise!

Savolitinib + Osimertinib

MET IHC3+/≥90% and/or FISH10+ population

ORR: 56%

mDoR: 7.1–9.9 mo

mPFS: 7.4–7.5 mo

Well tolerated (edema, nausea, diarrhea most common)

Clinically meaningful, durable responses. Precision-matched to MET-amplified/overexpressed tumors. Chemotherapy-sparing targeted option

Limitations:

Benefit confined to high MET expressers

Resistance still emerges

Phase III (SAFFRON) data awaited for practice change

SAVANNAH highlights the growing role of biomarker-driven therapy to tackle osimertinib resistance in EGFR+ NSCLC!”

“Major Breakthrough in Targeting TP53 Mutations! Rezatapopt (PC14586) reactivates the p53 Y220C mutant—a long-considered “undruggable” target in cancer.

Why it matters:

Restores wild-type p53 tumor suppressor function

Triggers antiproliferative effects in cancer cells

Shows potent single-agent and combo efficacy (incl. with immunotherapy)

Validated by deep structural and functional studies

Now in registrational Phase II trial for TP53 Y220C+ solid tumors

Significance: First-in-class agent with real potential to change the game for patients with p53-mutant cancers—a long-standing unmet need!”

“Breakthrough in Solid Tumor CAR-T Therapy!

Engineered scFvs precisely target mutant KRAS (G12V)

Neoantigen-specific CAR-Ts (NeoCARs) show strong in vitro and in vivo anti-tumor activity

Smart ‘armored’ NeoCARs with inducible IL-12 boost antigen presentation and cytotoxicity

TCR knockout – improved safety in vivo

Significance: Tackles the holy grail of solid tumors—KRAS-mutant cancers—offering a next-gen modular CAR-T platform with enhanced precision, efficacy, and safety for lung, pancreas, and RCC tumors.”