Background E39, an HLA‐A2‐restricted, immunogenic peptide derived from the folate‐binding protein (FBP), is overexpressed in multiple malignancies. We conducted a phase I/IIa trial of the E39 + GM‐CSF vaccine with booster inoculations of either E39 or E39′ (an attenuated version of E39) to prevent recurrences in disease‐free endometrial and ovarian cancer patients(pts). Here, we present the final 24‐month landmark analysis. Patients and methods HLA‐A2 + patients receiving E39 + GM‐CSF were included in the vaccine group (VG), and HLA‐A2‐ pts (or HLA‐A2 + patients refusing vaccine) were followed as the control group (CG). VG group received 6 monthly inoculations as the primary vaccine series (PVS) and were randomized to receive either E39 or E39′ booster inoculations. Demographic, safety, immunologic, and disease‐free survival (DFS) data were collected and evaluated. Results Fifty‐one patients were enrolled; 29 in the VG and 22 in the CG. Fourteen patients received <1000 μg and 15 received 1000 μg of E39. There were no clinicopathologic differences between VG and CG or between dose groups. E39 was well tolerated. At the 24 months landmark, DFS was 55.5% (VG) vs 40.0% (CG), P = 0.339. Patients receiving 1000 μg and boosted patients also showed improved DFS ( P < 0.03). DFS was improved in the 1000 μg group after treatment of primary disease (90.0% vs CG:42.9%, P = 0.007), but not in recurrent patients. In low‐FBP expressing patients, DFS was 100.0% (1000 μg), 50.0% (<1000 μg), and 25.0% (CG), P = 0.029. Conclusions This phase I/IIa trial reveals that E39 + GM‐CSF is safe and may be effective in preventing recurrence in high‐risk ovarian and endometrial cancer when optimally dosed (1000 μg) to FBP low patients being treated for primary disease.

The dendritoma vaccine has minimal toxicity profile with potential clinical benefit. There was OS advantage for NED stage IV patients, those receiving higher number of doses and increased frequency. Based on these results, we initiated a phase IIb trial utilizing improved dendritoma technology in the adjuvant setting for NED stage III/IV melanoma patients.

BACKGROUNDFolate binding protein(FBP) is an immunogenic protein over-expressed in endometrial(EC) and ovarian cancer(OC). We are conducting a phase I/IIa trial of E39 (GALE 301)+GM-CSF, an HLA-A2-restricted, FBP-derived peptide vaccine to prevent recurrences in disease-free EC and OC patients. This interim analysis summarizes toxicity, immunologic responses, and clinical outcomes to date.METHODSHLA-A2+ patients were vaccinated(VG), and HLA-A2- or -A2+ patients were followed as controls(CG). Six monthly intradermal inoculations of E39+250mcg GM-CSF were administered to VG. Demographic, safety, immunologic, and recurrence rate(RR) data were collected and evaluated.RESULTSThis trial enrolled 51 patients; 29 in the VG and 22 in the CG. Fifteen patients received 1000mcg E39, and 14 received <1000mcg. There were no clinicopathologic differences between groups(all p = 0.1). E39 was well-tolerated regardless of dose. DTH increased pre- to post-vaccination (5.71.5 mm vs 10.33.0 mm, p = 0.06) in the VG, and increased more in the 1000mcg group (3.82.0 mm vs 9.53.5 mm, p = 0.03). With 12 months median follow-up, the RR was 41% (VG) vs 55% (CG), p = 0.41. Among the 1000mcg patients, the RR was 13.3% vs 55% CG, p = 0.01. Estimated 2-year DFS was 85.7% in the 1000mcg group vs 33.6% in the CG (p = 0.021).CONCLUSIONSThis phase I/IIa trial reveals that E39+GM-CSF is well-tolerated and elicits a strong, dose-dependent in vivo immune response. Early efficacy results are promising in the 1000 mcg dose cohort. This study proves the safety and establishes the dose of E39 for a larger prospective, randomized, controlled trial in HLA-A2+ EC and OC patients to prevent recurrence.

Background Androgen deprivation therapy (ADT) is prescribed to almost half of all men diagnosed with prostate cancer. Although ADT is effective treatment, with virtually all men with advanced disease showing initial clinical response, it is associated with troublesome side effects including hot flushes and night sweats (HFNS). HFNS can be both frequent and severe and can have a significant impact on quality of life (QoL). They can occasionally be so debilitating that patients stop ADT altogether, despite the increased risk of disease relapse or death. Previous research has found that guided self-help cognitive behavioural therapy (CBT) can be effective in reducing HFNS due to ADT when delivered by a clinical psychologist. MANCAN2 aims test whether we can train the existing NHS Prostate Cancer Nurse Specialist (CNS) team to deliver guided self-help CBT and whether it is effective in reducing the impact of HFNS in men undergoing ADT. Methods MANCAN2 is a phase III multicentre randomised controlled trial and process evaluation. Between 144 and 196 men with prostate cancer who are currently receiving ADT and are experiencing problematic HFNS will be individually randomised in a 1:1 ratio in groups of 6–8 participants to either treatment as usual (TAU) or participation in the guided self-help CBT intervention plus TAU. A process evaluation using the normalisation process theory (NPT) framework will be conducted, to understand the CNS team’s experiences of delivering the intervention and to establish the key influencers to its implementation as a routine practice service. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost-effectiveness of the intervention and participant adherence to the trial intervention will also be assessed. Discussion MANCAN2 will advance the program of work already conducted in development of management strategies for HFNS. This research will determine whether the severity of ADT-induced HFNS in men with prostate cancer can be reduced by a guided self-help CBT intervention, delivered by the existing NHS prostate cancer CNS team, within a multicentre study. The emphasis on this existing team, if successful, should facilitate translation through to implementation in routine practice. Trial registration ISRCTN reference 58720120. Registered 13 December 2022