Bicycle has a wobble

Bicycle, already facing the tough task of competing against Astellas and Pfizer’s Padcev in first-line urothelial cancer, hasn’t reassured investors with its latest data on zelenectide pevedotin. The company claimed a 60% ORR with a Keytruda combo from the uncontrolled phase 1/2 Duravelo-1 trial – less than the 68% seen with Padcev plus Keytruda in the pivotal EV-302 trial

And 60% with zelenectide is generous, given that most of these responses are not confirmed, and it’s unclear if they ever will be. Bicycle apparently sees a future in bladder cancer, but spent much of a conference call last week outlining a biomarker strategy in breast and lung cancers, and beyond.

Unimpressed investors sent the company’s stock down 31% on Friday.

Bladder blip

Duravelo-1 has enrolled patients with various tumour types. On Thursday after market Bicycle said that, among 20 first-line cisplatin-ineligible urothelial cancer patients receiving zelenectide plus Keytruda, there were 12 responses.

However, only five of these were confirmed. When asked how many unconfirmed patients remained on therapy, and might therefore become confirmed, the group’s chief executive, Kevin Lee, only said that more information would be given at an upcoming medical meeting.

If just the confirmed responses are taking into account, this gives a much less impressive ORR of 25%.

Bicycle had already been facing questions about whether it might be able to gain accelerated approval for zelenectide, as hoped, given Padcev’s full approval in combo with Keytruda in first-line bladder cancer last year.

To support a potential accelerated nod Bicycle is carrying out the phase 2/3 Duravelo-2 trial, which is enrolling first and second-line bladder cancer patients. The company plans to report interim data from around 150 patients in the second half of 2025.

Nectin-4 amplification

Outside bladder cancer, the group is now targeting a biomarker strategy, and to this end reported more data from Duravelo-1, in breast and non-small cell lung cancers, suggesting improved efficacy in patients with Nectin-4 gene amplification.

In breast cancer Bicycle pointed to a 63% ORR among eight Nectin-4-amplified patients, versus 14% (5/35) in all-comers. One of these responses was unconfirmed. In NSCLC, 40% (2/5) Nectin-4-amplified patients responded, compared with 9% (3/34) in all comers. Again, one response was unconfirmed.

However, patient numbers are small, and the analyses were post-hoc.

Despite this Bicycle revealed plans to begin three new trials next year, all in second-line Nectin-4 amplified patients. Duravelo-3, in both ER-positive/HER2-negative and triple-negative breast cancer, is due to start in the first half. And Duravelo-4 in squamous and non-squamous NSCLC, and Duravelo-5 in various tumours including head and neck and ovarian, are both slated to begin in the second half.

Padcev has been investigated in other cancers, but hasn’t impressed. In the EV-202 trial, the ADC produced has shown response rates of 16-19% in breast cancer; results in NSCLC were even more lacklustre.

These results came in all-comers, and it seems possible that response rates with Padcev could also be improved with a similar biomarker strategy. However, Bicycle said it was building a “robust patent estate” relating to the use of Nectin-4 gene amplification.

In bladder cancer the company reckons it doesn’t need to use the biomarker, as Nectin-4 is highly expressed across all patients. Meanwhile, Nectin-4 amplification is seen in 20-30% of breast and lung cancer patients, and 10-20% of patients with “many other tumour types”, Bicycle said.