A phase 2 randomized study comparing telisotuzumab adizutecan monotherapy with standard of care in patients with post-adjuvant circulating tumor DNA–positive colorectal cancer.

TPS3688 Background: Curative intent standard of care (SOC) management of colorectal cancer (CRC) involves surgical tumor removal, followed by adjuvant therapy and active surveillance (AS). Presence of circulating tumor DNA (ctDNA) in the absence of radiographic evidence of disease is emerging as a reliable biomarker for determining molecular residual disease in CRC and in predicting recurrence after definitive therapy. Telisotuzumab adizutecan (Temab-A) is an antibody-drug conjugate that targets c-Met protein and is conjugated to a topoisomerase 1 (Top1) inhibitor payload. c-Met protein is ubiquitously expressed on CRC tumor cells. Temab-A has shown a manageable safety profile and promising antitumor activity in patients (pts) with advanced solid tumors, including CRC (NCT05029882). Herein, we describe a Phase 2 study of Temab-A monotherapy in pts with ctDNA-positive CRC after adjuvant therapy compared with AS. Methods: This open-label, randomized, global, multicenter, Phase 2 study (NCT07023289) includes adults (≥18 yrs) with histologically confirmed adenocarcinoma of the colon or rectum. Surgical tumor material must be available and submitted for Signatera personalized panel and assessment of c-Met protein levels. Pts must have received a total of ≥3 mos of perioperative and/or platinum-based doublet adjuvant therapy, have no radiographic evidence of disease as determined by CT scans and liver MRI, and be ctDNA-positive within the first year after the end of adjuvant therapy. Approximately 140 pts will be randomized (1:1) to receive either Temab-A (2.4 mg/kg, IV, Q3W, N=70) or AS only (N=70). Randomization will be stratified by oligometastatic versus nonmetastatic and by the timing of enrollment. Japan will have a separate randomization schedule stratified by the same factors. During 9 mos of treatment (12 cycles [C], 21 days [D] per C) or AS, pts will undergo monitoring for disease recurrence through CT scans (Q6W) and ctDNA testing (on C2D1, C3D1, C4D1, at 6 and 9 mos). Study follow-up will occur every 3 mos for the first 2 yrs and every 6 mos for the 3 yrs thereafter. The Table shows study objectives and endpoints. Clinical trial information: NCT07023289 . Objectives Endpoints Primary Evaluate efficacy of Temab-A Disease-free survival by investigator Secondary Evaluate clinical outcomes of Temab-A ctDNA clearance at 6 mos after randomizationOverall survival Safety Evaluate safety/tolerability of Temab-A Adverse event type, frequency, seriousness, and severityTreatment-emergent adverse events leading to treatment discontinuation and dose interruption Pharmacokinetics (PK) Evaluate PK and immunogenicity of Temab-A Serum concentration of:Temab-A conjugateTotal antibodyPlasma concentration of Top1 inhibitor