Table 4.
Efficacy and mutation detection
| A: Best response by cohort | S1 (n = 31) | S2 (n = 19) | S3 (n = 11) | NSCLC expansion (n = 14) | Total (n = 75) |
|---|---|---|---|---|---|
| Overall best response, n (%) | |||||
| Complete response (CR) | 0 | 0 | 0 | 0 | 0 |
| Partial response (PR) | 2 (6) | 1 (5) | 0 | 2 (14) | 5 (7) |
| Stable disease (SD) | 8 (26) | 12 (63) | 6 (55) | 7 (50) | 33 (44) |
| Progressive disease | 21 (68) | 6 (32) | 5 (45) | 5 (36) | 37 (49) |
| Overall response rate (CR + PR) | |||||
| n (%) | 2 (7) | 1 (5) | 0 | 2 (14) | NA |
| 95% CI | 0.8–21.4 | 0.1–26.0 | 0.0–28.5 | 1.8–42.8 | NA |
| Disease control rate (CR + PR + SD) | |||||
| n (%) | 10 (32) | 13 (68) | 6 (55) | 9 (64) | NA |
| 95% CI | 16.7–51.4 | 43.4–87.4 | 23.4–83.3 | 35.1–87.2 | NA |
| B: Mutation detectiona | |||||
|
| |||||
| Diagnosis | Linsitinib/erlotinib dose (mg) | Response (weeks) | ctDNA | Tumor DNA | |
|
| |||||
| S1 | |||||
| CRC | 400/150 | SD (6) | KRAS G12V, PIK3CA E542K | NA | |
| NSCLC (adenocarcinoma) | 450/150 | PR (72) | EGFR exon 19 del | NA | |
| Rectal (squamous) | 450/150 | PR (36) | NVD EGFR, KRAS, PIK3CA | NVD in EGFR, KRAS, BRAF, PIK3CA | |
| S2 | |||||
| Chordoma | 50/100 | PR (>268) | PIK3CA exon 9 E542K | NVD EGFR exons 18 – 21b, PIK3CA exon 9, BRAF exon 15 | |
| Expansion NSCLC | |||||
| Adenocarcinoma | 150 BID/150 | SD (6) | EGFR exon 19 del and T790M | NA | |
| Poorly diff adenocarcinoma | 150 BID/150 | PR (16) | NVD EGFR, KRAS | NA | |
| Adenocarcinoma | 150 BID/150 | SD (6) | KRAS G12D | KRAS G12D | |
| Adenocarcinoma | 150 BID/150 | PD | EGFR exon 19 del, T790M | NA | |
| Squamous | 150 BID/150 | PR (36) | NVD EGFR exons 18–21 | NVD | |
| Adenocarcinoma | 150 BID/150 | SD (30) | KRAS G12D | KRAS 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.
a
Mutation detection in ctDNA or archival tumor tissue, by cohort and dose (mg) of linsitinib/erlotinib.
b
Assay failure for exon 20 EGFR.