| Divarasib (GDC-6036) |
KRAS inhibitor |
Covalent inhibitor of KRAS G12C (switch II pocket) |
NSCLC & CRC (KRAS G12C+) |
ORR 53% (NSCLC); PFS 13.1 mo – Phase I/II |
C7-substitution (e.g., trifluoromethyl-pyridine) and warhead reactivity influence covalent binding to KRAS G12C |
| Glecirasib (JAB-21822) |
KRAS inhibitor |
Covalent KRAS G12C inhibitor |
Solid tumors (KRAS G12C+) |
ORR 48%, PFS 8.2 mo, OS ∼13.6 mo – Phase IIb |
1,8-Naphthyridine scaffold optimized for solubility and metabolic stability; enhances irreversible KRAS G12C inhibition |
| PRT543 |
Epigenetic inhibitor |
PRMT5 inhibitor (splicing and epigenetic regulation) |
Ovarian cancer, MDS |
CR in 1 ovarian case; responses in hematologic malignancies |
PRMT5 inhibitors with π–π interactions at Phe327; basic amines in pharmacophore tuned for selectivity and stability |
| Tulmimetostat (CPI-0209) |
Epigenetic inhibitor |
Dual EZH1/EZH2 inhibitor (chromatin modulation) |
ARID1A-mutant cancers |
∼25% PRs; thrombocytopenia, GI AEs (gastrointestinal adverse events) – Phase I/II |
EZH1/2 dual inhibition via chromatin interaction; SAR focuses on the methyltransferase domain and selective toxicity |
| Pegargiminase (ADI-PEG20) |
Enzyme therapy |
Depletes extracellular arginine in ASS1-deficient tumors |
Melanoma, glioblastoma |
SD 41–50%, PFS 3–5 mo, OS ∼8–11 mo – Phase I |
PEGylated arginine deiminase improves stability and tumor targeting in ASS1-deficient cancers |
|
225Ac-PSMA-R2 |
Radiopharmaceutical |
Actinium-225-labeled PSMA-targeted alpha emitter |
mCRPC (prostate cancer) |
PSA ≥50% decline in ∼47%, low toxicity – Phase I/II |
PSMA-targeting and alpha emitter tuning optimize selective radiation delivery with minimized hematologic toxicity |
| Scancell SCIB1 |
DNA vaccine |
Plasmid vaccine encoding TRP2/gp100 melanoma antigens |
Resected advanced melanoma |
100% OS at cut-off; 5 relapses only – Phase I/II |
Immunogenic TRP2/gp100 plasmid vaccine optimized for T-cell response and minimal off-target expression |
| Gridegalutamide |
PROTAC |
Androgen receptor degradation + antagonism |
mCRPC |
PSA declines; strong receptor degradation – Phase I |
Linker rigidity and AR binding domain shape enhance proteasomal degradation and androgen signaling blockade |
| Opaganib (ABC294640) |
SK2 inhibitor |
Inhibits sphingosine kinase 2 |
Solid tumors |
Some synergy with chemo – Phase II/III |
Selective SK2 inhibition achieved by hydrophobic core tuning and solubility-driven modifications |
| Sapacitabine |
Nucleoside analog |
DNA synthesis inhibitor, induces SSBs in S-phase |
AML, MDS (elderly/unfit patients) |
ORR 30–45%, OS ∼30% at 1 year – Phase II |
S-Phase selective analog design ensures DNA incorporation; substitutions influence chain termination and SSB induction |
| KappaMab (MDX-1097) |
Monoclonal antibody |
Targets kappa-light chain on MM cells |
Relapsed/refractory multiple myeloma |
ORR 83% with combo; OS benefit – Phase IIb |
Targeting epitope binding and antibody engineering improves MM cell selectivity and immune-mediated killing |
| Glesatinib (MGCD-265) |
TKI (type II MET) |
Dual MET and SMO kinase inhibitor |
MET-amplified NSCLC |
ORR ∼15%, low efficacy – Phase II |
Type II MET inhibition via DFG-out stabilization; scaffold substitutions failed to improve efficacy in MET-amplified tumors |
