Amivantamab with or without chemotherapy in right-sided metastatic colorectal cancer: Updated results from OrigAMI-1, an open-label, phase 1b/2 study.
Authors: Raghav Kanwal Pratap Singh , Van Cutsem Eric , Arnold Dirk , Oberstein Paul Eliezer , Lee Myung Ah , Cruz-Correa Marcia , Chen Eric Xueyu , Han Sae-Won , Malik Rozita Abdul , Eng Cathy , Moreno Victor , Chowdhury Sanjib , Iwasawa Ryota , Schnepp Robert W. , Bhattacharya Rianka , Lorenzini Patricia A , Baig Mahadi , Pietrantonio Filippo , Hecht Joel R 
Published: January 2025

197

Background:
Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity and is FDA approved in
EGFR
-mutated advanced non-small cell lung cancer. High MET expression is observed in ~68% of patients (pts) with metastatic colorectal cancer (mCRC). Additionally, MET amplification occurs in up to 23% of EGFR-resistant mCRC and is implicated in driving resistance to EGFR-targeting antibodies (EGFRi). Compared to left (L)-sided disease, right (R)-sided disease is less responsive to EGFRi and associated with poorer outcomes. We present longer follow-up data among pts with R-sided mCRC.
Methods:
OrigAMI-1 (NCT05379595) is assessing ami as monotherapy and combined with chemotherapy in mCRC. All pts were wild-type for
KRAS
,
NRAS
,
BRAF
, and
EGFR
ectodomain by central ctDNA testing, without
ERBB2
/
HER2
amplification. One ami monotherapy cohort (Cohort C) enrolled only pts with R-sided disease (all pts must have 2-3 prior lines; prior EGFRi allowed). The ami plus chemotherapy cohorts (Cohorts D [with FOLFOX] and E [with FOLFIRI) enrolled both L- and R-sided disease (1 prior line max; prior EGFRi use was exclusionary). Primary tumor locations of cecum, ascending colon, hepatic flexure, and transverse colon were considered R-sided. Response was assessed by the investigator per RECIST v1.1.
Results:
As of 26-Aug-2024, 23 pts with R-sided mCRC received ami monotherapy (median follow-up of 8.1 months [mo]). Median number of prior lines was 2, and 43% had prior EGFRi. There were 7 pts with R-sided disease who received ami plus FOLFOX or FOLFIRI (median follow-up of 6.5 mo); all 7 had received 1 prior line. Among pts receiving ami monotherapy, objective response rate (ORR) was 22% (5/23) and disease control rate (DCR) was 78% (18/23), with 1 achieving a complete response. Median duration of response (DoR) is 7.4 mo; response and treatment are ongoing for 3 of the 5 responders. In pts receiving ami plus FOLFOX or FOLFIRI, ORR was 43% (3/7) and DCR was 86% (6/7). Median DoR is 5.8 mo, with all 3 responders on treatment, of which 2 are ongoing response. Additional details are in the Table. Biomarker data will be presented at the meeting. Safety profile among R-sided disease was consistent with prior reports, with the most common ami-related grade 3+ AEs being rash and hypoalbuminemia (2 pts each).
Conclusions:
Ami monotherapy or combined with FOLFOX or FOLFIRI demonstrated durable antitumor activity in R-sided mCRC.
Clinical trial information: NCT05379595
.

Efficacy.

Ami monotherapy (n=23)
Ami + FOLFOX or FOLFIRI (n=7)

Median follow-up, mo (range)
8.1 (0.6–17.5)
6.5 (3.2–8.8)

Median number prior lines
2
1

Prior EGFRi, n (%)
10 (43)
0

ORR, % (95% CI)
22 (8–44)
43 (10–82)

Median DoR, mo (95% CI)
7.4 (3.7–NE)

5.8 (NE–NE)
a

DCR, % (95% CI)
78 (56–93)
86 (42–100)

Median progression-free survival, mo (95% CI)
3.7 (3.4–5.5)
7.4 (1.8–NE)

a
All 3 responders remain on treatment; 2 of 3 responders are ongoing response.