Scancell faces its big decision

Apparently promising early results last year with Scancell’s DNA-based immunotherapy SCIB1 only provided a temporary boost to the UK group’s stock. Reality has likely hit investors, with the company still needing to carry out a controlled phase 2/3 trial and, more immediately, raise the cash to fund this.

In the next few months Scancell will report further data from the same first-line melanoma study, Scope, with both SCIB1 and its next-generation contender, iSCIB1+. The results should help determine which project to take into a planned phase 2/3 trial – although Scancell is already leaning towards iSCIB1+, its chief executive officer, Lindy Durrant, tells ApexOnco.

SCIB1 vs iSCIB1+

Both projects use DNA to encode an antibody that incorporates the epitopes TRP-2 and gp100, which when expressed by antigen-presenting cells aim to stimulate a T-cell response. SCIB1 is restricted to around 40% of patients with specific haplotype, but iSCIB1+ can be used in all patients, Durrant states.

iSCIB1+ could also be more potent and, importantly for Scancell, has a longer patent life (patent expiry in 2040 versus 2028 for SCIB1). So far, however, the company has only reported data on SCIB1.

The uncontrolled Scope trial in unresectable melanoma found that 11 of 13 patients receiving SCIB1 plus Opdivo and Yervoy had a response, giving an ORR of 85%. By way of a benchmark, Scancell points to a 50% ORR with Opdivo plus Yervoy based on real-world data. Still, these are small patient numbers.

Q3 vs Q4

The third quarter will see more data on SCIB1, from 43 patients in the second stage of Scope (a number that will include the original 13 patients). 

Meanwhile, the first results with iSCIB1+, also from 43 patients, are now due in the fourth quarter, delayed from the first half. In both cases Scancell hopes to see an ORR of at least 63%.

As iSCIB1+ has “everything that SCIB1 has” and more, “we’re anticipating that iSCIB1+ will be better”, says Durrant, although she adds: “But clinical trials are always there to catch you out.”

This is why Scancell wants data on both before deciding which to take into an adaptive phase 2/3 trial, which could start in the first half of 2025. The design still needs to be nailed down with regulators, but Durrant says it will likely involve around 100 phase 2 patients, who would then roll over into a 300-patient phase 3 part. Half would receive SCIB1/iSCIB1+ plus Opdivo and Yervoy, and half the doublet alone.

Other developers of such immunotherapies have plumped for a Keytruda combo, notably BioNTech and Roche with autogene cevumeran, as well as IO Biotech, which is also gunning for first-line melanoma with its contender, IO102-IO103. Moderna and Merck are also testing their mRNA-4157 with and without Keytruda, but are focused on adjuvant melanoma.

However, Durrant is convinced that Opdivo/Yervoy is the right choice, saying that this produces better response rates, if patients can tolerate the toxicity.

Scope also gave physicians the choice of administering SCIB1/iSCIB1+ alongside Keytruda, but has only managed to recruit four patients to this combo arm. “That tells you how much the clinicians prefer [Opdivo/Yervoy].”

Funds needed

Scancell hopes that PFS data from the trial's phase 3 portion will be enough for an accelerated nod, with overall survival results from the same study being used for full approval. 

But even getting this trial started will depend on fresh funding. Durrant admits that these types of immunotherapies have a poor history, so "you probably need to do a randomised phase 2 to get a partner".

Scancell’s market cap sits at just £92m, so raising money from existing investors won't be easy either.