Table 4.

Efficacy and mutation detection

A: Best response by cohortS1 (n = 31)S2 (n = 19)S3 (n = 11)NSCLC expansion (n = 14)Total (n = 75)
Overall best response, n (%)
Complete response (CR)00000
Partial response (PR)2 (6)1 (5)02 (14)5 (7)
Stable disease (SD)8 (26)12 (63)6 (55)7 (50)33 (44)
Progressive disease21 (68)6 (32)5 (45)5 (36)37 (49)
Overall response rate (CR + PR)
n (%)2 (7)1 (5)02 (14)NA
95% CI0.8–21.40.1–26.00.0–28.51.8–42.8NA
Disease control rate (CR + PR + SD)
n (%)10 (32)13 (68)6 (55)9 (64)NA
95% CI16.7–51.443.4–87.423.4–83.335.1–87.2NA
B: Mutation detectiona
DiagnosisLinsitinib/erlotinib dose (mg)Response (weeks)ctDNATumor DNA
S1
CRC400/150SD (6)KRAS G12V, PIK3CA E542KNA
NSCLC (adenocarcinoma)450/150PR (72)EGFR exon 19 delNA
Rectal (squamous)450/150PR (36)NVD EGFR, KRAS, PIK3CANVD in EGFR, KRAS, BRAF, PIK3CA
S2
Chordoma50/100PR (>268)PIK3CA exon 9 E542KNVD EGFR exons 18 –21b, PIK3CA exon 9, BRAF exon 15
Expansion NSCLC
Adenocarcinoma150 BID/150SD (6)EGFR exon 19 del and T790MNA
Poorly diff adenocarcinoma150 BID/150PR (16)NVD EGFR, KRASNA
Adenocarcinoma150 BID/150SD (6)KRAS G12DKRAS G12D
Adenocarcinoma150 BID/150PDEGFR exon 19 del, T790MNA
Squamous150 BID/150PR (36)NVD EGFR exons 18–21NVD
Adenocarcinoma150 BID/150SD (30)KRAS G12DKRAS G12D
  • Abbreviations: adeno, adenocarcinoma; BID, twice daily; CI, confidence interval; CRC, colorectal cancer; diff, differentiated; NA, not available; NSCLC, non–small cell lung cancer; NVD, no variant detected; poorly diff, poorly differentiated; sq, squamous.

  • aMutation detection in ctDNA or archival tumor tissue, by cohort and dose (mg) of linsitinib/erlotinib.

  • bAssay failure for exon 20 EGFR.