Rybrevant accelerates expansion into solid tumors

Demonstrates 47% ORR in head and neck cancer… Emerges as a potential later-line treatment option

Expands into CMS4 colorectal cancer… demonstrated its dual-targeting mechanism

ASCO venue (Source: ASCO).

Johnson & Johnson’s EGFR-MET bispecific antibody Rybrevant (amivantamab) is expanding its development program beyond lung cancer into new solid tumor indications, including colorectal cancer and head and neck cancer.

Major clinical data for Rybrevant in solid tumors were presented at the 2026 American Society of Clinical Oncology (ASCO 2026) Annual Meeting, which was held recently in Chicago.

While Rybrevant has steadily expanded its presence in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC), the company is now broadening its research focus to a variety of solid tumors in which EGFR and MET signaling pathways play important roles.

In particular, attention is rising over the possibility of future label expansion, as meaningful clinical outcomes have been observed in patient populations with limited treatment options or in those who have not achieved sufficient benefit with existing EGFR inhibitors.

High response rates in head and neck cancer… shows potential as a later-line treatment alternative

The most notable findings came from a study involving recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Although treatment outcomes for recurrent or metastatic HNSCC have improved following the introduction of immuno-oncology drugs and platinum-based chemotherapy, treatment options remain limited after disease progression. In particular, patients with HPV-unrelated disease tend to have poor prognoses, creating an ongoing need for new treatment alternatives.

The Phase Ib/II OrigAMI-4 study evaluated subcutaneous (SC) Rybrevant monotherapy in 102 patients with HPV-unrelated recurrent or metastatic HNSCC whose disease had progressed after treatment with PD-(L)1-based immunotherapy and platinum-based chemotherapy.

The analysis showed an objective response rate (ORR) of 47%. Four patients achieved a complete response (CR), while 44 achieved a partial response (PR). Tumor reduction in target lesions was observed in 79% of patients.

Responses were also rapid. The median time to first response was 6.6 weeks, while the median duration of response (DOR) was 7.2 months. Median progression-free survival (PFS) was 6.8 months.

Industry experts believe these results compare favorably with those of Merck’s EGFR-targeted therapy ‘Erbitux (cetuximab),’ which is currently used in this setting. According to previously published data cited by the investigators, Erbitux demonstrated an ORR of 24% and a median PFS of 3.8 months in a comparable patient population.

The high rate of tumor shrinkage was also noteworthy. In the study, 79% of all patients experienced reductions in target lesions.

The safety profile was consistent with that found in Rybrevant studies. The most common adverse events included hypoalbuminemia, rash, acneiform dermatitis, paronychia, stomatitis, and fatigue. Treatment-related reactions occurred in 13% of patients, but were all Grade 1 or 2. The treatment discontinuation rate due to treatment-related adverse events (TRAEs) was 6%.

Company seeks to gain first-line indication for head and neck cancer … Phase III development underway

Johnson & Johnson is also conducting a global Phase III trial on Rybrevant’s use in the first-line treatment setting for recurrent or metastatic HNSCC.

The OrigAMI-5 study is a Phase III trial evaluating Rybrevant in combination with Keytruda (pembrolizumab) and carboplatin in approximately 500 patients with HPV-unrelated recurrent or metastatic HNSCC. The regimen is being directly compared with the current standard-of-care combination of Keytruda, platinum-based chemotherapy, and 5-FU.

Although Keytruda-based regimens are currently considered the standard first-line treatment for recurrent or metastatic HNSCC, response rates and long-term survival outcomes remain limited. Investigators are looking into whether adding Rybrevant could improve outcomes, given the high levels of EGFR and MET expression observed in head and neck cancer.

The study will be conducted at approximately 205 sites across 22 countries worldwide. Co-primary endpoints are ORR and overall survival (OS). Additional endpoints include PFS, DOR, and patient-reported outcomes (PROs).

Given that Rybrevant monotherapy achieved a 47% ORR in patients whose disease had progressed after immunotherapy and platinum-based chemotherapy in the OrigAMI-4 study, attention is now turning to whether the Phase III results could potentially alter future treatment strategies for head and neck cancer.

Demonstrates activity in CMS4 colorectal cancer… Highlighting the potential of MET-targeted therapy

Johnson & Johnson's ‘Rybrevant’

In colorectal cancer, new data suggest that Rybrevant may help overcome some of the limitations associated with existing EGFR inhibitors.

The OrigAMI-1 study evaluated Rybrevant monotherapy in patients with metastatic colorectal cancer lacking KRAS, NRAS, BRAF, and EGFR extracellular domain mutations, as well as HER2 amplification. All participants had previously received second- or third-line treatment in the metastatic setting.

This analysis focused on Consensus Molecular Subtypes (CMS), one of the major molecular classification systems for colorectal cancer.

CMS2 is a classic subtype characterized by high EGFR dependency and is known to respond well to EGFR inhibitors. In contrast, CMS4 exhibits mesenchymal characteristics associated with MET signaling activation and is known for its poor prognosis and generally limited responsiveness to EGFR inhibitors.

Previous studies reported that disease control rates (DCR) with Erbitux monotherapy were 68% in CMS2 patients but only 29% in CMS4 patients.

However, Rybrevant demonstrated relatively consistent efficacy across both subtypes.

Median PFS was 4.2 months in CMS2 patients and 5.3 months in CMS4 patients. Median OS was 11.3 months and 13.5 months, respectively, showing no major differences between the groups.

ORR was 26% in CMS2 patients and 16% in CMS4 patients, while DCR reached 83% and 74%, respectively. According to the investigators, treatment outcomes were also generally consistent regardless of tumor location.

The researchers concluded that Rybrevant maintained antitumor activity even in CMS4 subtypes, which are less dependent on EGFR signaling, based on the drug’s dual-target inhibition effect that targets both EGFR and MET pathways.

Because CMS4 is widely recognized as a subtype associated with resistance to conventional EGFR inhibitors, the findings are being viewed as evidence supporting the clinical value of a strategy that targets MET alongside EGFR.