Table 2.
Representative Basket and Umbrella Trials
| Study | Tumor types | Screening platform | Biomarkers tested | Drugs | Endpoint/results |
|---|---|---|---|---|---|
| BATTLE NCT00409968, NCT00411671, NCT00411632, NCT00410059, NCT00410189 Prospective, adaptively randomized, umbrella trial | Chemorefr actory NSCLC | non-NGS, mutation analysis, FISH, IHC; | mutation/ amplification: EGFR, KRAS/BRAF, CCND1; protein expression: VEGF, RXR, cyclinD1 | erlotinib, sorafenib, vandetanib, erlotinib + bexarotene | Better DCR for EGFR+erlotini b and KRAS/BRAF +sorafenib; |
| BATTLE-2 NCT01248247 2-stage Phase II umbrella design | Advanced NSCLC | NGS; DNA, mRNA, RPPA, IHC | IHC: pAKT, PTEN, HIF1a, LKB1; Mutation: P13KCA, BRAF, AKT1, HRAS, NRAS, MEK1, MET, CTNNB1, LKB1; | Erlotinib (ctrl) sorafenib, MK-2206+erlotinib; MK-2206+ selumetinib | 8-week disease control rate |
| Lung-MAP NCT02154490 Randomized Phase II/III umbrella design | Advanced, recurrent squamous cell lung carcinoma | FMI Foundatio nOne platform; IHC; | PI3KCA, CDK4/6, CCND1/2/3, FGFR1/2/3, HGF/c-MET | taselisib, palbociclib, AZD4547, erlotinib, erlotinib+rilotumu mab, ipilimumab, nivolumab, durvalumab | PFS, ORR, OS |
| I-SPY-2 NCT01042379 Randomized open label Phase II umbrella design (adjuvant setting) | Stage III breast cancer | Conventio nal, MRI; | HER2, hormone receptor, and Mammaprint; Bayesian marker-adaptive trial designs | HER2+: Neratinib, MK2206+Trastuzu mab, T-DM1+Pertuzumab, Trebananib +Trastuzumab, Pertuzumab+ Trastuzumab HER2−: veliparib, MK2206, Ganitumab+metfor min, Trebananib | Pathological complete response; Several drugs graduated to Phase III trials [229–231] |
| ALCHEMIST NCT02194738; NCT02193282; NCT02201992; NCT02595944 Screening study and accrual to Phase III randomized treatment studies (adjuvant setting) | Resectable non-squamous NSCLC | NGS, tissue and blood; germline + somatic alteration s | EGFR mutation; ALK rearrangements (FISH); PD-L1 expression (IHC) | Erlotinib, Critozinib, Nivolumab | OS |
| SAFIR02 Breast NCT02299999 Phase II randomized umbrella design | HER2 negative recurrent and/or metastatic breast cancer | CGH array, hotspot sequencin g | To be determined during the study | AZD2014, AZD4547, AZD5363, Sapitinib Selumetinib, Vandetanib, Bicalutamide, Olaparib, durvalumab | PFS as compared to standard maintenance |
| SAFIR02 Lung NCT02117167 Phase II randomized umbrella design | EGFR and ALK WT recurrent and/or metastatic NSCLC | CGH array, hotspot sequencin g | To be determined during the study | AZD2014, AZD4547, AZD5363, Sapitinib Selumetinib, Vandetanib, durvalumab | PFS as compared to standard maintenance |
| Lung MATRIX NCT02664935 Phase II non-randomized umbrella design | Advanced, pretreated NSCLC | 28-gene NGS platform | Mutation: FGFR2/3, TSC1/2, LKB1, KRAS+RbWT, NF1, NRAS, PIK3CA, AKT1, EGFR+ EGFRT790 LoF: p16+RbWT, PTEN Amp: CDK4+RbWT, CCDN1+RbWT, MET, PIK3CA; Rearranged: ROS1 | AZD4547, AZD2014,Palbocicli b, Crizotinib, Selumetinib, AZD5363, Osimertinib, durvalumab | ORR, PFS |
| FOCUS 4 [232] PhaseII/III randomized umbrella design | Advanced/ metastatic, untreated colorectal cancer | Hotspot-seq biomarker only; IHC, | BRAF, PIK3CA, KRAS, NRAS; PTEN, MMR, | BRAFi+panitumum ab+/−MEKi, Aspirin, AKTi+MEKi, HER1/2/3i, | ORR, PFS, OS |
| V-BASKET [49] NCT01524978 flexible, early phase 2, basket study | Solid tumors, multiple myeloma | Mutation analysis with local method | BRAFV600 | Vemurafenib monotherapy; Vemurafenib + Cetuximab in CRC | Efficacy in NSCLC, ECD, and LCH |
| CUSTOM [47] NCT01306045 Biomarker-derived, Multiarm, Multihistology Phase II, basket trial | NSCLC, SCLC, thymic malignancy | NGS | Mutation: AKT1, BRAF, EGFR, ERBB2, HRAS, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN; Amplification: ERBB2, PIK3CA, PDGFRA; Fusion: ALK; | erlotinib, selumetinib, MK2206, lapatinib, sunitinib | Targeting EGFR and ALK offers benefit; design not feasible for most arms |
| NCI-MATCH NCT02465060 Non-randomized Phase II; basket trial | Advanced, recurrent, refractory solid tumors, lymphoma, myeloma | NGS (4000 variants across 143 genes) | Mutations: AKT1, BRAF V600; BRAF non V600, BRCA1/2, cKIT, DDR2, dMMR, EGFR, EGFRT790M, FGFR1/2/3, GNAQ/GNA11, HER2, MET ex14 sk, mTOR, NF1, NRAS, PI3KCA, PTEN, SMO/PTCH1, TSC1/2;Transloc ations: ROS1, ALK; Amplification: CCDN1/2/3, CDK4/6, HER2, MET; Loss: NF2, PTEN; Fusion: NFRK | Ado-trastuzumab emtansine, Afatinib, AZD4547, AZD5363, AZD1775, Osimertinib, Binimetinib, Crizotinib, Dabrafenib+tramet inib, Dasatinib, Defactinib, GSK2636771, Larotectinib, Nivolumab, Palbociclib, Sunitinib, TAK-228, Taselisib, Trametinib, Trastuzumab, Vismodegib | ORR |
AZD4547, FGFR inhibitor; AZD5363, AKT1/2/3 inhibitor; AZD1775, WEE1 inhibitor; AZD2014, inhibitor of mTORC1/2; CGH, comparative genomic hybridization; ECD, Erdheim-Chester disease; GSK2636771, inhibitor of PI3K beta; LCH, Langerhans’ cell histiocytosis; NGS, next generation sequencing; MK2206, inhibitor of AKT1/2/3; NSCLC, non small cell lung cancer; OS, ocerall survival; ORR, overall response rate; PFS, progression free survival; RPPA, reverse phase protein array; SCLC, Small cell lung cancer; TAK-228, dual mTORC1/2 inhibitor;