PublishedNovember 2, 2026
JournalClinical Cancer Research
TrialEMB01X201, phase Ib/II, NCT05176665

EGFR/c-MET Bispecific Antibody EMB-01 Shows Early Activity (12.5% Confirmed Response) in Heavily Pretreated Metastatic Colorectal Cancer in a Single-Arm Phase Ib/II Trial

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Article Summary
  • EMB01X201 was a multicenter, open-label, single-arm phase Ib/II trial at 13 sites in China and the United States of EMB-01, a tetravalent EGFR/c-MET bispecific antibody, given at 1,600 mg intravenously once weekly. Of 52 patients treated, 48 had metastatic colorectal cancer (median 3 prior lines of therapy). Confirmed objective response rate was 12.5% (6/48; 95% CI, 4.7%–25.2%), disease control rate 64.6% (95% CI, 49.5%–77.8%) and median PFS 15 weeks (95% CI, 10.6–23.3).
  • In a prespecified favorable subgroup (left-sided, RAS/RAF wild-type, no prior fruquintinib, regorafenib or TAS-102; n = 29), confirmed ORR was 20.7% (95% CI, 8%–39.7%) and median PFS 19 weeks (95% CI, 12.3–24.1). All responses occurred in this subgroup. Grade ≥3 treatment-related adverse events occurred in 63.5% of patients. The trial was nonrandomized and had no comparator arm, so it cannot establish that the activity is attributable to dual EGFR/c-MET inhibition.

Why This Study Matters

For patients with metastatic colorectal cancer (mCRC) whose disease has progressed on standard therapy, options in the third line and beyond are limited. The authors note that the approved late-line agents regorafenib, fruquintinib and trifluridine–tipiracil (TAS-102) have demonstrated objective response rates (ORR) of only 1% to 5%.

One recognized mechanism of acquired resistance to anti-EGFR antibodies is activation of the c-MET pathway, described in the paper as occurring in approximately 20% of patients with mCRC after progression on anti-EGFR therapy. EMB-01 is a tetravalent bispecific antibody (bsAb) built on a Fabs-in-tandem platform that binds both EGFR and c-MET, with the aim of blocking both signals in a single molecule.

1
Overall mCRC cohort (n = 48): confirmed ORR 12.5% (6/48; 95% CI, 4.7%–25.2%), disease control rate 64.6% (95% CI, 49.5%–77.8%), median PFS 15 weeks (95% CI, 10.6–23.3).
2
Prespecified favorable subgroup (left-sided, RAS/RAF wild-type, no prior fruquintinib/regorafenib/TAS-102; n = 29): unconfirmed ORR 24.1% (95% CI, 10.3%–43.5%), confirmed ORR 20.7% (95% CI, 8%–39.7%), median PFS 19 weeks (95% CI, 12.3–24.1).
3
All responses were observed in the favorable subgroup.
4
Safety: grade ≥3 treatment-related adverse events occurred in 63.5% of patients, led by rash (25%) and dermatitis acneiform (17.3%).

Study Design

This was a multicenter, open-label, single-arm phase Ib/II trial conducted at 13 sites in China and the United States. Phase II used a Bayesian optimal two-stage design, with phase Ib data included. All treated patients received EMB-01 1,600 mg intravenously once weekly in 28-day cycles, for up to 2 years, until progression, death, unacceptable toxicity or withdrawal. Tumor response was assessed per RECIST v1.1.

Primary endpoints: safety and tolerability in phase Ib, and antitumor activity in phase II. Exploratory endpoints included biomarker analyses. The analysis of the favorable subgroup was prespecified in the statistical analysis plan. There was no randomization and no comparator arm. The sponsor was EpimAb Biotherapeutics Co. Ltd. (per the paper's competing-interest statement).

Trial at a glance

52 patients enrolled (phase Ib: 27; phase II: 25); 48 with mCRC (41 China, 7 US); 13 sites; EMB-01 1,600 mg IV once weekly; single-arm, no randomization.

Patient Population

Between April 7, 2022 and September 4, 2025, 180 patients were prescreened or screened; 128 (71.1%) did not meet eligibility criteria and 52 (28.9%) were enrolled and treated. Forty-eight (92.3%) had colorectal cancer; the others had gastric (1), hepatocellular (1) or biliary tract (2) cancer.

Among the 48 patients with mCRC, median age was 58.5 years (range, 40–76); 21 (43.8%) had ECOG performance status 0 and 27 (56.3%) had status 1. They were heavily pretreated, with a median of 3 prior lines of therapy (range, 1–11). Prior exposure included anti-VEGF therapy in 38 (79.2%), anti-EGFR therapy in 32 (66.7%) and both in 26 (54.2%). Thirteen (27.1%) had previously received fruquintinib, regorafenib or TAS-102. Forty-four (91.7%) had left-sided primary tumors, and all but one were RAS/RAF wild-type.

Primary Endpoint Results

OutcomeFavorable subgroup (n = 29)Overall mCRC (n = 48)
Confirmed ORR20.7% (6/29; 95% CI, 8%–39.7%)12.5% (6/48; 95% CI, 4.7%–25.2%)
Unconfirmed ORR24.1% (7/29; 95% CI, 10.3%–43.5%)14.6% (7/48; 95% CI, 6.1%–27.8%)
Disease control rate82.8% (24/29; 95% CI, 64.2%–94.2%)64.6% (31/48; 95% CI, 49.5%–77.8%)
Clinical benefit rate55.2% (16/29; 95% CI, 35.7%–73.6%)41.7% (20/48; 95% CI, 27.6%–56.8%)
Median PFS19 weeks (95% CI, 12.3–24.1)15 weeks (95% CI, 10.6–23.3)
Median DOR (confirmed responses)32 weeks (95% CI, 16–not estimable), both groups combined32 weeks (95% CI, 16–not estimable)

No complete responses were observed. Among the 48 patients, confirmed best response was partial response in 6 (12.5%), stable disease in 25 (52.1%) and progressive disease in 13 (27.1%); 4 (8.3%) had no response assessment done.

EMB-01 demonstrated a manageable safety profile and promising antitumor activity in heavily pretreated mCRC, particularly in the RAS/RAF wild-type, left-sided mCRC subgroup naïve to late-line therapies, warranting further clinical development.
— Abstract, Clinical Cancer Research (DOI 10.1158/1078-0432.CCR-26-2128)

Subgroup Analyses

The paper reports ORRs across prespecified subgroups of the favorable cohort (n = 29) with a forest plot; the overall ORR for this population was 24.1%. The authors state that every subgroup confidence interval overlapped the overall ORR and that the study was not powered to detect differences between subgroups. The figures below are taken from the Results text and should be read as hypothesis-generating.

SubgroupORR, n/NComparisonORR, n/N
ECOG 030.8% (4/13)ECOG 118.8% (3/16)
Age <6527.3% (6/22)Age ≥6514.3% (1/7)
Asian23.1% (6/26)Non-Asian33.3% (1/3)
Male25% (6/24)Female20% (1/5)
No liver metastasis25% (3/12)Liver metastasis23.5% (4/17)
1–2 prior lines33.3% (3/9)≥3 prior lines20% (4/20)
Anti-EGFR naïve27.3% (3/11)Prior anti-EGFR22.2% (4/18)
Anti-VEGF naïve50% (2/4)Prior anti-VEGF20% (5/25)
Diagnosis within 24 months42.9% (3/7)Diagnosis >24 months ago18.2% (4/22)

Stratified by anti-EGFR exposure, median PFS was 23.9 weeks (95% CI, 10.6–35.7) in anti-EGFR–naïve patients versus 17.8 weeks (95% CI, 11.7–30) in pretreated patients. Among patients with a washout of ≥8 months from prior anti-EGFR therapy (n = 16), uORR was 25% (95% CI, 7.3%–52.4%) and median PFS 18 weeks (95% CI, 7–30); the two patients with a shorter interval had no objective responses (median PFS 13.6 weeks; 95% CI, 12.3–NA).

Biomarkers (exploratory, overall mCRC cohort): no clear association was seen between baseline EGFR or c-MET protein expression and response. Patients with MET amplification had a numerically higher ORR than those without (33.3% [2/6] vs. 9.5% [4/42]), and a lower baseline ctDNA alteration burden (<3 alterations) was associated with better outcomes. The authors caution that sample sizes were small.

Safety Profile

Safety was evaluated in all 52 treated patients (median treatment duration 11.1 weeks; range, 0.1–55). All patients (100%) had at least one treatment-emergent adverse event (TEAE) and 51 (98.1%) had at least one treatment-related adverse event (TRAE). Grade ≥3 TEAEs occurred in 37 patients (71.2%) and grade ≥3 TRAEs in 33 (63.5%). TEAEs led to treatment discontinuation in four patients (7.7%); two patients (3.8%) discontinued because of TRAEs (flank pain and dermatitis acneiform). Infusion-related reactions occurred in five patients (9.6%), all grade 1–2. Edema, a recognized c-MET–related toxicity, occurred in three patients (5.8%), all grade 1–2.

Preferred termTRAEs, n (%)Grade ≥3 TRAEs, n (%)
Rash (grouped term)32 (61.5)13 (25)
Myalgia28 (53.8)1 (1.9)
Paronychia20 (38.5)4 (7.7)
Hypoalbuminemia18 (34.6)1 (1.9)
Alanine transaminase increased15 (28.8)1 (1.9)
Dermatitis acneiform12 (23.1)9 (17.3)

Rash is defined in the source as a grouped term that includes dermatitis acneiform, folliculitis, papular rash, drug eruption, eczema, papule, pustular rash and stoma site rash; dermatitis acneiform is therefore also counted within the rash line. N = 52 for all rows.

Interpretation and Broader Context

The authors conclude that EMB-01 has a manageable, on-target safety profile (cutaneous toxicities consistent with EGFR inhibition) and promising activity in heavily pretreated mCRC, supporting randomized trials in the third-line setting, evaluation in MET-amplified mCRC and combination strategies.

Cross-study context (not a within-trial comparison): the authors compare their favorable subgroup (confirmed ORR 20.7%; median PFS 4.4 months) with the CRICKET trial of cetuximab plus irinotecan rechallenge in a strictly selected population (ORR 21%; 95% CI, 10%–40%; median PFS 3.4 months; 95% CI, 1.9–3.8). They also compare the overall cohort (cORR 12.5%; median PFS about 3.5 months) with historical standard third-line results of ORR 1% to 4.7% and median PFS 1.9 to 3.7 months. These are indirect comparisons across different populations and should not be read as head-to-head results.

Limitations

The authors state that the trial was nonrandomized, open-label and had no comparator arm; subgroup analyses were not powered for comparison; it is unknown whether the efficacy reflects the favorable prognosis of a highly selected population; and the activity cannot be definitively attributed to dual EGFR/c-MET inhibition. One patient with a KRAS K117N mutation was enrolled. The trial therefore could not establish whether EMB-01 improves outcomes relative to standard late-line therapy.

Trial registration

Primary source: DOI 10.1158/1078-0432.CCR-26-2128 · PubMed 42635595 · PMC13725330

References

  1. Xu T, Parseghian CM, Zhang Y, et al. EMB-01, an Anti-EGFR/c-MET Bispecific Antibody, in Patients with Heavily Pretreated Metastatic Colorectal Cancer from a Phase Ib/II, Open-Label, Multicenter Study. Clin Cancer Res. 2026. doi: 10.1158/1078-0432.CCR-26-2128. PMID: 42635595. PMCID: PMC13725330.
  2. ClinicalTrials.gov: NCT05176665.