Abstract 1087P
Background
KL-6 and SP-D have been used to assess lung injury with anticancer therapies, including tyrosine kinase inhibitors (TKIs). We evaluated the predictive value of KL-6 and SP-D for lung adverse event incidence and their variation during mobocertinib treatment (tx) as a readout of lung inflammation.
Methods
Plasma and serum samples were collected at baseline (BL), Cycle 3, Day 1 (C3D1), and Cycle 5, Day 1 (C5D1) from previously treated pts with EGFR ex20ins+ mNSCLC who received mobocertinib 160 mg orally once daily in a phase 1/2 study (NCT02716116). KL-6 and SP-D, measured by ELISA, were analyzed in pts who developed pneumonitis vs those who did not and by response to mobocertinib (partial response [PR], stable disease [SD], or progressive disease [PD]). KL-6 and SP-D ratios from BL to C3D1 were analyzed by response (PR/SD or PD). KL-6 ratios between BL and C3D1 and BL and C5D1 were evaluated by best tumor change in target lesions.
Results
BL KL-6 was lower in pts with no pneumonitis (n=87) vs pts with pneumonitis on mobocertinib (n=5; P=0.039) but distribution of values overlapped (table). Only 1 pt with pneumonitis had available BL SP-D. During mobocertinib tx (BL to C3D1), KL-6, unlike SP-D, decreased in pts with PR (P<0.0001) or SD (P<0.0001) but not in pts with PD (P=1.0). Low KL-6 ratio (BL to C3D1) was associated with best overall response (BOR; Table; P=0.01); SP-D ratio (BL to C3D1) was not associated with BOR (P=0.28). Low KL-6 ratios (BL to C3D1 and BL to C5D1) were associated with IRC-assessed responses at corresponding timepoints (P=0.02).
Conclusions
BL KL-6 and SP-D did not predict pneumonitis in pts with mNSCLC. KL-6 decreased in pts with PR and SD but not in pts with PD, and KL-6 ratio was linked to response to mobocertinib. Monitoring circulating KL-6 as a sign of therapeutic benefit may be warranted for pts with mNSCLC on TKI tx. Table: 1087P
KL-6 and SP-D in patients receiving mobocertinib
| KL-6 (U/mL) BL Median (IQR) | SP-D (ng/mL) BL Median (IQR) | |
| No pneumonitis | 626 (403–1505) (n=87) | 211 (115–404) (n=73) |
| Pneumonitis | 2552 (1029–3338) (n=5) | 415 (415–415) (n=1) |
| P value (Wilcoxon) | 0.039 | 0.40 |
| PR | 475 (345–736) (n=18) | 162 (114–290) (n=16) |
| SD | 577 (345–1526) (n=28) | 210 (123–422) (n=22) |
| PD | 618 (454–1029) (n=9) | 415 (284–574) (n=9) |
| P value (Kruskal-Wallis) | 0.57 | 0.42 |
| KL-6 (U/mL) OR (95% CI) | SP-D (ng/mL) OR (95% CI) | |
| Ratio (BL to C3D1) and BOR | 17.1 (2.0–inf) | 2.2 (0.4–inf) |
| P value (Fisher exact) | 0.01 | 0.28 |
inf, infinity; IQR, interquartile range; OR, odds ratio.
Clinical trial identification
NCT02716116.
Editorial acknowledgement
Professional medical writing assistance was provided by Amy Zannikos, PharmD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Takeda Development Center Americas, Inc., Lexington, MA, USA.
Legal entity responsible for the study
Takeda Development Center Americas, Inc.
Funding
Takeda Development Center Americas, Inc.
Disclosure
Z. Su, X. Tong, V. Bunn, S. Jin, S. Vincent: Financial Interests, Personal, Full or part-time Employment: Takeda.