655O Phase Ib study of cofetuzumab pelidotin, an anti-PTK7 antibody-drug conjugate, in patients with PTK7-expressing recurrent non-small cell lung cancer (rNSCLC)

Cofetuzumab pelidotin (Cofe-P), a protein tyrosine kinase 7 (PTK7)–targeting antibody-drug conjugate, was tolerable and had preliminary antitumor activity in patients (pts) with advanced solid tumors (Phase 1; NCT02222922). Results are presented from an ongoing Phase 1b, open-label, single-arm, multicenter study (NCT04189614) of Cofe-P in pts with PTK7-expressing rNSCLC. Eligible pts were ≥18 yrs with PTK7-expressing (central immunohistochemistry [IHC]) rNSCLC and prior platinum doublet and immune checkpoint inhibitor (tumors w/o actionable genetic alterations [AGA−]) or platinum doublet and targeted agent(s) (AGA+ tumors). Pts received 2.8 mg/kg Cofe-P IV Q3W until PD/unacceptable toxicity. As of August 9, 2022, 56 pts received Cofe-P (median age, 64 years; male, 63%; Asian, 50%, White, 46%); 27 pts (48%) were nonsquamous (NSQ) EGFR WT, 13 (23%) were NSQ EGFR mutant, and 16 (29%) were squamous (SQ). PTK7 IHC enrollment cutoff was refined during study; 42 pts (75%) had PTK7 expression above final ≥90%/≥2+ cutoff; of these, 21 (50%) were NSQ EGFR WT. Enrollment of SQ and NSQ EGFR mutant pts was halted to prioritize NSQ EGFR WT accrual due to response rates in each subgroup. Efficacy results are shown in the table. TEAEs were reported in all pts, most common (≥30%): alopecia (52%), neutropenia (45%), headache (36%), pruritis (36%), and decreased appetite (30%). Grade ≥3 TEAEs were reported in 68% of pts, most common (≥5%): neutropenia (39%), leukopenia (9%), pneumonia (7%), anemia (5%), fatigue (5%). Peripheral neuropathy was reported in 18% of pts; 2% had Grade 3. No deaths related to Cofe-P were reported. PK was similar to previous phase 1 study with Cofe-P conjugate elimination half-life ∼3 days.Table: 655OParameterNSQ EGFR WT, PTK7 ≥90%/≥2+ N=21Overall N=56ORR, % (95% CI)30.0 (11.9, 54.3)a19.6 (10.2, 32.4)CBR (CR + PR + SD), % (95% CI)90.0 (68.3, 98.8)a78.6 (65.6, 88.4)mDOR, mo (95% CI)5.8 (2.8, –)7.2 (2.8, 9.7)mPFS, mo (95% CI)5.5 (2.6, 8.5)5.3 (3.6, 5.9)aResponse-evaluable pts (N=20) (≥1 postbaseline measurement). CI, confidence intervals; CBR, clinical benefit rate; CR, complete response; EGFR, epidermal growth factor; mDOR, median duration of response; mPFS, median progression free survival; NSQ, nonsquamous; ORR, objective response rate; PR, partial response; PTK7, protein tyrosine kinase 7; pts, patients; SD, stable disease; WT, wild type. Open table in a new tab aResponse-evaluable pts (N=20) (≥1 postbaseline measurement). CI, confidence intervals; CBR, clinical benefit rate; CR, complete response; EGFR, epidermal growth factor; mDOR, median duration of response; mPFS, median progression free survival; NSQ, nonsquamous; ORR, objective response rate; PR, partial response; PTK7, protein tyrosine kinase 7; pts, patients; SD, stable disease; WT, wild type. Cofe-P was well-tolerated with encouraging antitumor activity observed in rNSCLC and 30% ORR in the subpopulation with NSQ EGFR WT NSCLC and PTK7 ≥90%/≥2+.