Johnson & Johnson’s (J&J’s) bispecific Rybrevant (amivantamab) could provide an effective, novel option for patients with head and neck squamous cell cancer (HNSCC), an expert has said.
This follows the positive results of the Phase Ib/II OrigAMI-4 study (NCT06385080), which saw the subcutaneous therapy trigger an objective response rate (ORR) of 45%. Of these patients, one achieved a complete response (CR), while 12 achieved partial responses (PR).
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Stable disease was experienced by 15 patients in the Rybrevant monotherapy arm, meaning that 82% of patients given the drug experienced a clinical benefit.
The median duration of response (DoR) to Rybrevant monotherapy was 7.2 months. Overall survival (OS) has not yet matured.
Meanwhile, the bispecific was generally well tolerated, with the most common treatment-emergent adverse events (TEAEs) being rash, fatigue and hypoalbuminaemia.
Following the positive outcome of the OrigAMI-4 trial, J&J is taking Rybrevant to late-stage trials in first-line HNSCC. Currently, the big pharma company is recruiting patients for the Phase III OrigAMI-5 study, which will look at Rybrevant’s potential alongside Merck’s Keytruda (pembrolizumab) and platinum-based chemotherapy in HPV-unrelated HNSCC.
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By GlobalDataRybrevant’s triple threat
In conversation with Pharmaceutical Technology, Henar Hevia, Senior Director, EMEA therapeutic area lead of oncology at J&J, noted that the company had high hopes for Rybrevant in HNSCC and beyond due to its ability to change both the disease’s “trajectory and pathology”. According to Hevia, this means that the drug can prevent mutations and improve long-term survival.
Rybrevant primarily achieves this through its three-pronged mechanism of action (MoA), which sees the bispecific target the epidermal growth factor (EGFR) and mesenchymal-epithelial transition (MET) receptors, while also activating the immune system.
Through its disease activity within recurrent or metastatic (R/M) HNSCC, Hevia and the Innovative Medicines team at J&J are hoping to “set a new standard of care (SoC) with Rybrevant” in the HNSCC indication, which the OrigAMI-5 study could facilitate.
New treatments would likely be welcomed by HNSCC patients, as the five-year survival for those diagnosed with the indication currently sits at 15%, with one-third of patients failing to make it to second-line treatment.
Addressing EGFR overexpression
Though Rybrevant has shown promising activity in R/M HNSCC, the bispecific had its first roots in non-small cell lung cancer (NSCLC), which is often associated with EGFR mutations.
After getting approval from the US Food and Drug Administration (FDA) in EGFR Exon 20-mutated NSCLC in 2021, the drug was later granted full approval in certain NSCLC subsets in 2024.
Since then, Rybrevant plus chemotherapy has become a cornerstone of the second-line treatment paradigm for the disease. However, it may soon progress to the front-line setting, as recent data from the Phase III MARIPOSA study revealed that the drug is superior to the current SoC, Tagrisso (osimertinib), when combined with EGFR inhibitor, Lazcluse (lazertinib).
However, J&J saw potential in the drug across a range of solid tumour indications, including HNSCC and colorectal cancer, which are also characterised by high EGFR mutation rates.
“Amongst the HNSCC patient population, EGFR overexpression can be seen in between 80% to 90% of cases, so it makes a lot of sense to investigate Rybrevant in this setting,” Hevia stated.
Thus far, J&J’s assessments of Rybrevant in this setting seem to be paying off, as so far, “progression-free survival (PFS) and ORR rates are higher than the drugs currently available in this setting, while the same is true for duration of response (DoR),” said Hevia. “These are promising efficacy results”.
The New Jersey pharma hopes to add to its streak of successes in colorectal cancer too, as the company is currently recruiting for the OrigAMI-2 trial, which will look at the drug in combination with chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6).
