Two trials within CRUK Combinations Alliance portfolio transition to their Expansion Phase

23 Jul 2018
Announcement

In June 2018, two currently open trials within the CRUK Combinations Alliance Portfolio  have successfully defined their recommended phase 2 dose within the Dose Escalation Phase of the Trial, and have now opened their randomised expansion cohorts to patients in the target cancer type and setting via the ECMC network.

SPIRE

  • Combination - DNA hypomethylating agent SGI-110+cisplatin+gemcitabine
  • CI-Dr Simon Crabb (Southampton)
  • Sponsor and CTU – Southampton
  • Combinations Alliance Partner -Astex Pharmaceuticals
  • Dose Escalation - Any solid tumour – completed
  • Dose Expansion - Neoadjuvant bladder cancer - recruiting

SPIRE’s escalation phase, has been completed exclusively through the ECMC network, with additional recruiting sites at Sheffield (PI Sarah Danson), and the Royal Marsden (PI Robert Huddart).

Together with Southampton they have recruited 19 patients in a period of 22 months, to define the recommended phase 2 dose to take forward. The expansion cohort was opened in June, and the first patient was quickly recruited in Southampton.

Patients will be randomised in a 1:1 ratio to either receive SGI-110 in combination with cisplatin and gemcitabine, or cisplatin and gemcitabine alone, before radical cystectomy.  

Another 3 sites are in setup (Guys, Preston and Imperial), with 10 intended in total (including contingency sites) to support recruitment to the expansion phase to complete the recruitment of 20 neo-adjuvant bladder cancer patients within a 12-month period.

SPIRE was showcased at ASCO this year, through a Trials In Progress Poster. The dose escalation data is expected to be presented in a poster at the 2018 ESMO meeting.

FAK-PD1

  • Combination – defactinib (FAK inhibitor) and pembrolizumab (PD-1 immunotherapy)
  • CI- Dr Stefan Symeonides (Edinburgh)
  • Sponsor and CTU: Glasgow
  • Combinations Alliance Partner -Verastem
  • Dose Escalation - Any solid tumour – completed
  • Dose Expansion - mesothelioma, non small cell lung (NSCLC) and pancreatic cancers - recruiting

FAK-PD1 is a phase I/II immunotherapy combination trial, exploring the addition of FAK inhibition (defactinib) to PD-1 blockade (pembrolizumab), supported by funding from Verastem, MSD and CRUK.

13 patients were enrolled over the 12 months of the dose escalation phase, across the FAK-PD1 team’s five ECMC network sites: Glasgow (Prof Jeff Evans), Leicester (Prof Dean Fennell), Southampton (Prof Christian Ottensmeier), Belfast (Dr Vicky Coyle), and Edinburgh.

Both dose levels were found to be safe, with some early signs of activity, and the 47 patient dose expansion phase opened for specific tumour groups (mesothelioma, NSCLC & pancreatic cancer) in June, and is predicted to take 12 months to complete recruitment.

Translational parts of the study will characterise the immune effects of defactinib and the combination, including all patients in the mesothelioma and NSCLC expansions having on-treatment biopsies (randomised 1:1 to having a defactinib monotherapy run in period or upfront combination therapy).