University of Colorado Cancer Center, Aurora, CO
D. Ross Camidge , Jair Bar , Hidehito Horinouchi , Jonathan W. Goldman , Fedor Vladimirovich Moiseenko , Elena Filippova , Irfan Cicin , Penelope Ann Bradbury , Nathalie Daaboul , Pascale Tomasini , Tudor-Eliade Ciuleanu , David Planchard , Mor Moskovitz , Nicolas Girard , Janet Yikai Jin , Martin Dunbar , Ellen Bolotin , Jim Looman , Christine Ratajczak , Shun Lu
Background: Teliso-V is an antibody-drug conjugate composed of a c-Met antibody (ABT-700) and a microtubule inhibitor (monomethyl auristatin E). The phase 2 M14-239 trial (LUMINOSITY, NCT03539536) aims to identify the c-Met OE NSCLC populations best suited to Teliso-V (Stage 1) and expand selected groups for further evaluation of efficacy (Stage 2). In Stage 1, pts were enrolled into cohorts defined by histopathology (non-squamous [NSQ] or squamous [SQ]) and EGFR mutation status (mutant or wild type [WT]); NSQ cohorts were further divided in groups on the basis of c-Met expression (high or intermediate). Updated data from the fourth interim analysis (IA4) are presented. Methods: Pts had locally advanced/metastatic NSCLC, ≤2 prior lines of systemic therapy, ≤1 line of chemotherapy, and tumors that were c-Met OE by central immunohistochemistry (IHC; Ventana; Tucson, AZ). c-Met OE was defined for the NSQ cohort as ≥25% 3+ by IHC (high, ≥50% 3+; intermediate, 25 to <50% 3+) and for the SQ cohort as ≥75% 1+ by IHC. The planned enrollment was up to approximately 150 pts in Stage 1 and 160 pts in Stage 2. Teliso-V was dosed at 1.9 mg/kg IV Q2W. The primary endpoint is objective response rate (ORR) by independent central review. Secondary endpoints include duration of response (DOR). Results: As of data cutoff (27 May 2021), 136 pts were treated with Teliso-V; 122 were evaluable for ORR. ORR was 36.5% in the NSQ EGFR WT cohort (52.2% in c-Met high group and 24.1% in c-Met intermediate group), but was modest in the NSQ EGFR mutant and SQ cohorts. Efficacy data in groups/cohorts are in the Table. The most common any-grade adverse events (AEs) were peripheral sensory neuropathy (25.0%), nausea (22.1%), and hypoalbuminemia (20.6%). Grade 5 AEs considered possibly related to Teliso-V occurred in 2 pts (sudden death and pneumonitis in 1 pt each in the SQ cohort). Conclusions: Teliso-V demonstrated a promising ORR in pts with previously treated c-Met OE NSQ EGFR WT NSCLC; this cohort is currently expanding in Stage 2. ORR was modest in the cohorts of pts with c-Met OE NSQ EGFR mutant NSCLC and with c-Met OE SQ NSCLC; both cohorts have now met the protocol-specified stopping criteria and are no longer enrolling. The safety profile observed was consistent with IA3. Clinical trial information: NCT03539536.
NSCLC Group | Confirmed Responses (n/N) | ORR,% (95% CI) | Events/Responders | Median DOR, mo (95% CI) |
---|---|---|---|---|
c-Met OE NSQ EGFR WT | 19/52 | 36.5 (23.6, 51.0) | 8/19 | 6.9 (4.1, –) |
c-Met high | 12/23 | 52.2 (30.6, 73.2) | 5/12 | 6.9 (2.4, –) |
c-Met intermediate | 7/29 | 24.1 (10.3, 43.5) | 3/7 | – (4.1, –) |
c-Met OE NSQ EGFR mutant | 5/43 | 11.6 (3.9, 25.1) | 2/5 | – (3.0, –) |
c-Met high | 5/30 | 16.7 (5.6, 34.7) | 2/5 | – (3.0, –) |
c-Met intermediate | 0/13 | 0 (–, –) | 0 | Not applicable |
c-Met OE SQ | 3/27 | 11.1 (2.4, 29.2) | 2/3 | 4.4 (3.0, –) |
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Abstract Disclosures
2023 ASCO Annual Meeting
First Author: Fengying Wu
2023 ASCO Annual Meeting
First Author: Xiaorong Dong
2023 ASCO Annual Meeting
First Author: Hidehito Horinouchi
2022 ASCO Annual Meeting
First Author: Jonathan W. Goldman