Table 2. Some ongoing early clinical trials testing MTA in Molecularly-Selected Populations (MSP).
| Family of MTA | MTA | Target | Genetic alteration as inclusion criteria in Ph1 | Early signs of efficacy in Ph1 | Ref | Ongoing studies | ClinicalTrials.gov identifier |
|---|---|---|---|---|---|---|---|
| FGFR inhibitors | AZD4547 | FGFR1/2/3 | Yes, since escalation, FGFR1/2ampl |
No CR 2 PR (SqNSCLC FGFR1ampl, GC FGFR2ampl) SD (BC, GOJ/GC SqNSCL, UC FGFRampl) |
[76–78] | Ph1 Ph2 NSCLC Ph2 GC/GOJ Ph2 BC |
NCT00979134 NCT01824901 NCT01457846 NCT01202591 |
| BGJ398 | FGFR1/2/3 | Yes, since escalation, any FGFRalt | No CR 6 PR (4 UC FGFR3mut, 2 SqNSCLC FGFR1ampl) SD (BC FGFR1ampl, ABTC FGFR2transl) |
[79] | Ph1 Ph2 ABTC |
NCT01004224 NCT02160041 |
|
|
JNJ-42756493 (erdafitinib) |
FGFR1/2/3/4 | Yes, since escalation, any FGFRalt | 1 CR (UC FGFR2trunc) 1 PR (UC FGFR3transl) SD (lung, CS, BC FGFR1ampl) |
[80] | Ph1 Ph2 UC |
NCT01703481 NCT02365597 |
|
| MET inhibitors |
INC280 (capmatinib) |
MET | Yes, since escalation, METalt | No CR No PR SD (CRC, HCC, lung) |
[81] | Ph1 Ph2 NSCLC |
NCT01324479 NCT01911507 |
| SAR125844 | MET | Yes, since escalation, METalt | No CR 1 PR (lung cMETampl) SD (not specified) |
[82] | Ph1 Ph2 NSCLC |
NCT01391533 NCT02435121 |
|
| EGFR inhibitors |
PF-00299804 (dacomitinib) |
Pan-HER | Yes, since expansion, EGFRalt | No CR 4 PR (AdeNSCLC) SD (AdeNSCLC, others) |
[83] | Ph1 Ph2 OEC Ph3 NSCLC |
NCT00225121 NCT01608021 NCT01000025 |
| Multi-tyrosine kinase inhibitors |
E3810 (lucitanib) |
VEGFR1/2/3 PDGFRa/b FGFR1/2/3 |
Yes, since expansion, cohort FGFR1/11q ampl | 3 CR (2 MTC, 1 RCC) PR (NSCLC and BC FGFR1/11q ampl) SD (NSCLC and BC FGFR1/11q ampl, others) |
[84] | Ph1 Ph2 BC HR+ Ph2 NSCLC |
NCT01283945 NCT02053636 NCT02109016 |
|
PIK3CA/ mTOR pathway inhibitors |
BYL719 (alpelisib) |
PIK3CAa | Yes, since escalation, PIK3CAalt | No CR 15 PR (2 BC HR+ PIK3CAalt) |
[85] | Ph1 Ph2 BC HR+ |
NCT01219699 NCT02058381 |
|
BKM120 (buparlisib) |
Pan-Class I PIK3CA |
Yes, since expansion, cohort PIK3CA/PTENalt | No CR 4 PR (1 confirmed TBNC PI3KCAmut, 1 PGC, BC HR+,EH) |
[86] | Ph1 Ph2 TBNC |
NCT01068483 NCT01629615 |
|
| MAPK pathway inhibitors |
LGX818 (encorafenib) |
BRAF | Yes, since escalation, BRAF V600mut | No CR 13 PR (M BRAF V600mut), 12 SD (CRC BRAF V600mut) |
[87, 88] | Ph1 | NCT01436656 |
|
MEK162 (binimetinib) |
MEK1/2 | Yes, since expansion, KRAS and BRAFmut | No CR 1 PR (ABTC NRASmut), 9 SD |
[89] | Ph1 | NCT00959127 | |
| PARP inhibitors | olaparib | PARP | No, expansion enriched BRCAmut | 1 CR (BC) 21 PR (15 OC, 6 BC) |
[90] | Ph1 BC/OC Ph2 TBNC Ph3 OC |
NCT01445419 NCT02681562 NCT02446600 |
| talazoparib | PARP | Yes, since expansion, BRCAmut | No CR 13 PR (11 OC/peritoneal, 2 BC BRCAmut) |
[91] | Ph1 Ph2 BC |
NCT01286987 NCT02034916 |
|
| ROS/ALK inhibitors | X-396 | ALK | Yes, since escalation, ALKalt | No CR 5 PR (NSCLC ALKtransl) 5 SD (NSCLC ALKtransl) |
[92] | Ph1 | NCT01625234 |
|
RXDX-101 (entrectinib) |
Pan-TrKA/B/C ROS1 ALK |
Yes, since escalation, TrKA/B/C, ROS1 and ALKalt | No CR 4 PR (1 CRC TrKA+, 1 NSCLC ROS1+ and NSCLC ALK+, 1 NB ALK+) 2 SD (NSCLC ALK+, PC ROS1+) |
[93] | Ph1 | NCT02097810 |
Abbreviations: MTA (Molecularly Targeted Agents); HER 2 (Human Epidermal growth factor Receptor) 2; EGFR (Epidermal Growth Factor Receptor); ALK (Anaplastic Lymphoma Kinase); FGFR (Fibroblast Growth Factor Receptor); ampl (amplification); mut (mutation); trunc (truncation); transl (translocation); alt (alteration); HCC (HepatoCarcinoma); NSCLC (Non Small Cell Lung Cancer); Ade (Adenocarcinoma); Sq (Squamous); ALCL (Anaplastic Large-Cell Lymphoma); BC (Breast Cancer); HR+ (Hormone Receptor positive); CS (ChondroSarcoma); OEC (OEsophageal Carcinoma); GOJ (GastroesOphageal Junction carcinoma); GC (Gastric Cancer); UC (Urothelial Carcinoma); MTC (Medullary Thyroid Carcinoma); RCC (Renal Clear Cell carcinoma); M (Melanoma); CRC (ColoRectal Cancer); ABTC (Advanced Biliary Tract Carcinoma); OC (Ovarian Carcinoma); TBNC (Triple Breast Negative Cancer); PGC (Parotid Gland Carcinoma); EH (Epithelioid Hemangiothelioma); NB (NeuroBlastoma); PC (Pancreatic Carcinoma); CR (Complete Response); PR (Partial Response); SD (Stable Disease); VEGFR (Vascular Endothelial Growth Factor Receptor); PDGFR (Platelet Derived Growth Factor Receptor); TrK (Tropomyosin receptor Kinase); PARP (Poly [ADP-ribose] polymerase); BRCA (BReast CAncer gene); Ph (Ph).