The Candidates List: Targets and Possible Therapies for Squamous Cell Carcinoma of the Lung
This article was originally published in RPM Report
Executive Summary
The Friends of Cancer Research has identified 16 potential molecular targets and nearly two dozen drugs in development for use in squamous cell carcinoma of the lung. Organizers of a master protocol registrational trial for SCCL hope to select four therapies to test when the study launches in 2014.
Potential Targets and Candidate Drugs
PD1 (Programmed death 1) and PD-L1 (Programmed death ligand 1) inhibitors
- Biomarker: PD1 is presumptive biomarker
- Candidate drug: PD-L1 blocking antibody (MEDI4736)(MedImmune)
IGF inhibitor
- Biomarker: Free circulating IGF1 levels
- Measured in blood=primary biomarker
- Ancillary tumor markers of IGFR
- Candidate: LDK378 (already in development as ALKi)(Novartis)
- Biomarker – IGFR expression by IHC from Ventana
Met inhibitor
- Biomarker: High MET expression (and EGFR for this purpose)
- Combination therapy: Met inhibitor + erlotinib
- Control would be erlotinib
- Candidate: MET TKI (AMG337) (Amgen)
- Candidate: small molecule met inhibitor (LY2801653) (Eli Lilly)
- Biomarker: RON, AXL, ROS1, DDR1-DDR2, TEK, MNKN1/2
- Candidate: met inhibitor JNJ38877605 (Janssen)
- Candidate: Foretinib (GSK1363089) (GSK)
HGF inhibitor
- Biomarker(s): High HGF expression
- Candidate: Rilotumumab (AMG102) (Amgen)
FGFR inhibitor
- Biomarker: FGFR expression (including amplification)
- Candidate: LY2874455 (Eli Lilly)
- Candidate: JNJ42756493 (Janssen)
- Candidate: FGF Trap - GSK3052230 (formally HGS1036)(GSK)
- Biomarker: FGFR1, FGF ligand, protein expression of FGF2, p-FGFR1, FRS-2
PI3K inhibitor
- Biomarker: PI3KCA expression (including amplification) and mutation
- Candidate: BKM120 (Novartis)
- Candidate: PI3Kα inhibitor (MLN1117) (Millennium)
- Candidate: GSK2110183 (AKT inhibitor)
- Biomarker: AKT fusions, PI3K fusions, p-AKT
Wee1 inhibitor
- Biomarker: p53 mutation
- Candidate: MK1775 (Merck)
- Gemcitabine as control (or docetaxel)
Anti-HDM2
- Biomarker: HDM2 amplified / P53wt
- Candidate: Anti-HDM2 (Sanofi)
RANK ligand Inhibitor
- Biomarker: RANK and/or RANK ligand expression
- Candidate: Denosumab (Amgen)
EGFR Inhibitor
- Biomarker: L858R, Del(19) and T790M EGFR mutations
- Candidate: oral EGFR inhibitor (CO1686)(Clovis)
CDK4/6 inhibitor
- Biomarker: Potentially KRAS
- Candidate: LY2835219 (Eli Lilly)
Notch inhibitor 2
- Biomarker: Notch mutations
- Candidate: LY3039478 (Eli Lilly)
MEK + PI3K inhibitor combination
- Biomarker: RAS mutations
- Candidate: MEKi (Merck Serono) + pan-PI3K (Sanofi)
Anti-HER3
- Biomarker: TBD; potential HER3 expression
- Candidate: HER3 mAb (Sanofi)
Dual mTOR inhibitor (used in combination)
- Biomarker: TBD
- Candidate: MLN0128 (Millennium)
Pan-Raf kinase inhibitor
- Biomarker: TBD
- Candidate: MLN2480 (Millennium)
Source: Friends of Cancer Research