Giannis Mountzios: 10 exciting compounds that will shape lung cancer in 2025

Giannis Mountzios, Consultant Medical Oncologist at the Department of Medical Oncology in the Air force General Hospital in Athens, shared a post on X:

“2024 has been an amazing year for lung cancer, mainly due to biotechnology breakthroughs leading to pivotal new drugs entering clinical arena.

In the thread below you can see (in reverse order) 10 EXCITING COMPOUNDS that, IMO will shape innovation in 2025.”

“No 10: ACANSULIMAB (BNT311/GEN1046)

Acasunlimab is a bi-specific Ab targeting both PD-L1 and 4-1BB (or CD137), a member of the TNF superfamily.

CD137 stimulation led to >50% DCR in ph1 as mono- or in combo with pembro, as presented in WCLC24.”

“No 9: SIGVOTATUG VEDOTIN (SGN-B6A)

SV is a novel ADC targeting Integrin-B6A in cancer cell surface delivering the potent cytotoxic MMAE through a protease-cleavable linker.

Yielded 33% cORR in non-SQ taxane-naive pts, rapidly moving to an ongoing ph3 trial against docetaxel in 2L setting.”

“No 8: BL-B01D1 EGFR X HER3 ADC

BL-B01D1 is a pivotal ADC targeting both EGFR and HER3, carrying a Topo1 inhibitor as a payload, with a DAR of 8.

Achieved 63.2% ORR in EGFRmut NSCLC pts with a median of 3 prior treat lines! Presented by Zang et al. in ASCO24. 57% Gr>=3 TRAEs.”

“No 7: ZONGERTINIB and BAY2927088 HER2mut TKIs

Zongertinib and BAY2927088 are both highly selective TKIs of HER2 activating mutations, including the YVMA insertion in exon 20. Both achieved ORR >70% in pretreated pts and are currently being tested in 1L (Beamion-Lung02/SOHO-02).”

“No 6: VOLRUSTOMIG

Bispecific Ab against PD1/CTLA4 Volrustomig combines double immune inhibition in one shot. Produces responses in 52% of NSq and 65% of Sq NSCLC and a median PFS of 7 months in pre-treated patients.76% Gr3-4 TRAEs.Currently in ph3 in 1L with chemo.”

“No 5: ZIPALERTINIB EGFR Exon 20ins TKI

Zipalertinib is an irreversible, oral EGFR TKI targeting EGFRex20ins mutations, showing an ORR of 38.4%, mPFS 10m and mDoR 10 m in heavily pretreated pts, including 40% ORR after amivantamab. Any G Rash in 90%, diarrhea 30%.”

“No 4: TELISOTUZUMAB VEDOTIN (ABBV-399) and TELISOTUZUMAB ADUZITECAN (ABBV-400):

ADCs against MET oncoprotein Teliso-V produced 28.6% ORR in NSQ EGFRwt c-Met+ NSCLC and 53% ORR in combo with Osi in EGFRmut, c-MET+ NSCLC.

Teliso-A has a more potent, TOPO1 payload, compared to V.”

“No 3: PATRITUMAB DERUXTECAN :

ADC targeting HER3 An ADC composed of patritumab, a MoAb against ErbB3, linked to the Topo1 inh DX 8951, a semisynthetic, derivative of camptothecin. Achieved 29.8% ORR in pts with EGFRmut NSCLC after 3rd Gen TKI and PBC, currently in ph 3 HERTHENA-Lung02.”

“No 2: IVONESCIMAB:

Bispecific Ab against PD1/VEGF Ivonescimab outperformed pembro in the random ph 3 study Harmoni-2 in pts with PDL1+tumors, including a mPFS of 11 m.

Already approved in China, currently in ph3 in 1L both as mono- in PDL1-high and with PBC in all comers.”

“No1: DLL3/T-cell Engagers (Tarlatamab/ Obrixtamig)

Those agents engage neuroendocrine cells expressing DLL3 to T-lymphocytes via TCR binding, boosting immune response.

Breakthrough FDA approval for Tarlatamab based on phase 2 data, including impressive ORR of 40% and mOS of 14.2 m in heavily pretreated pts. Phase 3 results vs SoC highly anticipated in 2025 A 2nd T-cell engager, obrixtamig, is in advanced clinical development.”

“If you liked the above list, feel free to RT, comment or add new compounds that may have been omitted.

Happy to share your thoughts!”