TABLE 3.
Detailed overview of 15 patients treated on SPRING trial
| ID#Age/SexDose level | Histology | Prior therapy (no.)Prior checkpoint blockade (Y/N) | PDL1 + IHC (%) a | TMB a | Genomic results (vendor) a | Best response | PFS (weeks) b | Any drug held or reduced in first 60 days c | DLT (yes or no) comment |
|---|---|---|---|---|---|---|---|---|---|
|
1 80/Flevel 1 |
Adenocarcinoma | 2:Y | 25% | Could not be determined | KRAS G12V, DNMT3A V675fsb38, MS could not be determined (FM) | SD | 27 | No | No |
|
2 52/Mlevel 1 |
Adenocarcinoma | 1:Y | 0% | Intermediate, 6 muts/Mb | FGFR4 amplification, KRAS G12V, Myc amplification equivocal, PIK3CB amplification, C11orf30 (EMSY) amplification equivocal, CCND3 amplification, EPHB1 amplification, PRKCI amplification, TERC amplification, TP53 K120fsb1, TSHR A623S, VEGFA amplification, MS stable (FM) | PR | 24 | No | No |
|
3 64/Flevel 1 |
Adenocarcinoma | 0:N | 60% | Not done | TP53 splice site 981_993 + 34del47, ERBB2 A775_G776insYVMA, ERRFI1 S138fsb8, ERRFI1 Q88b, MS not done (FM) | PR | 181+ | Yes, axitinib held | No |
|
19 80/Flevel 1 |
Adenocarcinoma | 1:Y | 0% | Low, 4 Muts/Mb | No alterations, MS stable (FM) | SD | 64 | No | No |
|
20 72/M level 1 |
Adenocarcinoma | 1:N | 0% | Low, 5 Muts/Mb | C17orf39 amplification, KMT2A (MLL) R1976Q, Myc amplification, RAD21 amplification, SMARCA4 R1189Q, STK11 K262, TP53 loss, MS stable (FM) | PD | 8 | No | No |
|
21 61/M level 1 |
Squamous | 1:Y | 5% | Intermediate, 6 Muts/Mb | SOX2 amplification, CDKN2A D108H, EP300 Y1414C, FGF12 amplification, NFE2L2 D29H, NTRK3 E412K, POLE K733N—subclonal TP53 C238W, VHL truncation intron 1, MS stable (FM) | SD | 15 | No | No |
|
5 69/Mlevel 2 |
Squamous | 1:N | 0% | Not done | P53, Ki67, RET.5p_NM_020975.4e6e7, MS not done (Histopath) | PD | 7 | Yes, course 2 delayed | No |
|
4 63/Mlevel 2 |
Adenocarcinoma | 2:Y | <1% | Not done | TP53 mutation, MS not done (Oncomine) | SD | 29 | Yes, palbociclib held | No |
|
9 68/Flevel 2 |
Undifferentiated large cell carcinoma | 2:Y | 60–70% | Not done | No mutations, MS not done (Sheba Medical Center In house test: INFINITI®EGFR assay and Ion Torrent PGM system) | Not evaluable e | Not evaluable e | Yes, avelumab discontinued |
Yes Avelumab infusion reaction |
|
11 67/Mlevel 2 |
Adenocarcinoma | 1:N | TPS <1% | Not done | No mutations, MS not done (Illumina TruSight) | SD | 18 | Yes, palbociclib held | No |
|
13 72/Mlevel 2 |
Adenocarcinoma | 1:N | 0% | Not done | EGFR, ALK and ROS1 negative, MS not done (Unknown vendor) | PR | 25 | Yes, course 2 delayed | No |
|
10 51/Mlevel 2 |
Adenocarcinoma | 1:Y | 70% | Not done | No mutations, MS not done (Illumina TruSight) | PR | 14 | No | No |
|
15 76/Mlevel 3 |
Squamous | 1:Y | Not done | Not done | Not done | SD | 6 | Yes, palbociclib reduced |
Yes Respiratory failure d |
|
14 51/Mlevel 3 |
Large cell neuroendocrine | 2:Y | 0% | Intermediate, 11 Muts/Mb |
AR1D1A G328fsb35, STK11, LRPIB, KEAP, NFI, CCND1 amplification, KRAS amplification, FGF19 amplification, FGF3 amplification, FGF4 amplification (FM) MS stable (Caris) |
SD | 11 | Yes, palbociclib and axitinib held |
Yes Grade 3 fatigue and palmar‐plantar erythrodysesthesia |
|
16 54/Flevel 3 |
Adenocarcinoma | 2:Y | 50% | Low, 4 Muts/Mb | FAT1 D3519fsb13, TET2 K542fsb19, TP53 TI55fsb26, MS Stable (FM) | SD | 24 | Yes, axitinib held | No |
Abbreviations: DLT, dose‐limiting toxicity; F, female; FM, Foundation Medicine; IHC, immunohistochemistry; M, male; mb, megabase; MS, microsatellite; muts, mutations; N, no; PFS, progression‐free survival; TMB, tumor mutation burden; TPS, tumor proportion score; Y, yes.
Genomic results, TMB, and PDL1 may have been obtained as part of routine care; results were obtained prior to SPRING trial.
“+” sign indicates ongoing PFS (data cutoff April 8, 2021 for PFS assessment).
Drugs might be held or dose reduced because of Grade 2 side effects, in addition to Grade 3 or greater side effects.
DLT was death due to respiratory failure possibly drug related.
Not evaluable because patient did not receive full course of therapy; had infusion reaction to avelumab with first dose. Further, withdrew consent during course 2.