Australian research featured on the program at the 2025 ESMO Congress in Berlin ranged across cancer types; from basic science, to early studies of novel therapeutics, and phase 3 RCTs.

Durvalumab doesn’t impress in mesothelioma

Professor Anna Nowak, from the University of WA, presented primary results from the DREAM3R study of durvalumab with chemotherapy as first-line treatment in advanced pleural mesothelioma.

Professor Anna Nowak

The study follows promising results in 2020 and 2021 from the phase two DREAM [link here] and PrEO505 [link here] trials of the combination of durvalumab plus pemetrexed and either cisplatin or carboplatin for pleural mesothelioma.

She told the meeting that as discussions about the phase 3 DREAM3R trial were underway, the Checkmate 743 trial of nivolumab plus ipilimumab versus chemotherapy found first-line immunotherapy delivered an overall survival benefit (18.1 v 14.1 months; HR 0.74; p=0·0020). [link here]

“However, this benefit was less apparent in the 75% of patients who had epithelioid histology with a hazard ratio of 0.86 and the confidence interval crossing unity. As such, it was considered appropriate to continue with the DREAM3R trial testing durvalumab plus chemotherapy versus chemotherapy as a control arm.”

Professor Nowak said DREAM3R struggled with slow recruitment and did not reach full enrollment, likely due to a combination of factors including the global COVID-19 pandemic and the influence of Checkmate 743.

She reported on 174 mostly male patients, aged about 71 years, with mostly (93%) epithelioid histology.

The study found no significant difference in overall survival (21 v 18 months; HR 0.92; p = 0.92) or PFS (8 v 7 months; HR 0.70; p = 0.20) between chemotherapy plus durvalumab and chemotherapy alone arms.

However the objective tumor response rate for chemotherapy plus durvalumab was 58% versus 35% for chemotherapy alone (p = 0.005).

“The high objective tumor response rate and tumor control for chemotherapy plus durvalumab raises the potential that this could be a regimen that could be tested in neoadjuvant therapy prior to surgery for mesothelioma,” Professor Nowak said.

Meanwhile she said the issues with study recruitment precluded definitive conclusions and its time had passed given chemotherapy alone would no longer be considered standard of care.

“I’ll conclude by pointing out that timely activation of randomised phase three trials after positive phase two trials is critically important to seize the window of opportunity for accrual and provide reliable answers.”

Vaccine promising in advanced melanoma

Professor Adnan Khattak, from the Edith Cowan University in Perth, presented phase 2 data on the use of a personalised peptide-based neoantigen vaccine EVX-01 in addition to pembrolizumab in 16 patients with advanced unresectable melanoma and no prior therapy.

Professor Adnan Khattak

Pembrolizumab 400 mg IV was given from the start of the trial every six weeks for a maximum period of two years. Six priming doses of EVX-01 were given every two weeks from week 12 followed by four booster doses at weeks 30, 42, 54, and 78.

The study was deemed feasible with 100% manufacturing success.

Regarding safety, UVX-01 monotherapy was fairly well tolerated with no grade ≥3 adverse events. Most AEs were grade 1, including fatigue, injection site reactions and myalgia. In combination with pembrolizumab, there were no new safety signals and only one grade 3/4 AE of pancreatitis and diabetic ketoacidosis.

The objective response rate of the cohort, based on change in target lesion size, was 75% with four complete responders and eight partial responders. One patient maintained stable disease and three progressed.

The study found 54% of responses deepened with the introduction of EVX-01 at week 12, including three partial responders converting to a complete response.

“92% of the responders continue to respond at the 24-month time point, suggesting a durability of response,” he said.

Four patients dropped out of the trial – three due to progressive disease and one partial responder due to a spontaneous intracranial hemorrhage unrelated to the disease.

Professor Khattak said EVX-01 induced potent vaccine-specific T cell responses in 81% of patients which were sustained through the 2-year study period.

“These findings support the ongoing development of this combination, and further discussions are ongoing with sponsors and regulatory authorities,” he concluded.

Breast cancer protection from childbearing explained

Professor Sherene Loi, from the Peter MacCallum Cancer Centre, presented novel findings helping to explain the known protective effect of parity and breastfeeding on the risk of breast cancer in women.

Professor Sherene Loi

The research, also published in Nature [link here], showed that a full cycle of pregnancy, breastfeeding, and breast recovery induced an accumulation of CD8+ T cells within human normal breast tissue.

“These cells act like local guards, ready to attack abnormal cells that might turn into cancer. This protection may have evolved to defend mothers during the vulnerable post-pregnancy period, but today it also lowers breast cancer risk, especially the aggressive type called triple-negative breast cancer,” she said in a Peter Mac statement.

“We also studied data from over 1,000 breast cancer patients and found women who breastfed had tumours with higher numbers of these protective T cells and, in some groups, they lived longer after diagnosis of breast cancer.”

Professor Loi said the findings offer new insights into breast cancer prevention and treatment.

Non-chemotherapy option fails in advanced gastric cancer

Meanwhile Dr David Goldstein, on behalf of the Australasian Gastro-Intestinal Trials Group, presented results of the first phase 3 study of regorafenib plus nivolumab versus chemotherapy in patients with refractory advanced gastric or gastro-oesophageal cancer.

Despite some promising survival benefits of adding regorafenib to best supportive care in the recently published INTEGRATE II study [link here], the INTEGRATE IIb of regorafenib and nivolumab failed to show a survival benefit.

Overall survival (5.9 v 6.3 months; HR 0.88; p=0.23) and progression free survival (1.9 v 1.9 months; HR 0.85) were similar in both arms while the 12-month disease control rate was numerically but not significantly higher with regorafenib and nivolumab (14% v 0%).

“The proven survival benefit of regorafenib monotherapy compared with placebo in this setting, along with the numerically higher objective response rate and disease control rate among responders with REGORNIVO, encourages the search for more effective non-chemotherapy combinations, potentially with regorafenib as the backbone,” he concluded.

“All our patients are asking us, especially those who are still of good performance status, what’s next? Unfortunately, this particular combination is not going to be one of them.”

Other Australians on the ESMO program included:

• Associate Professor Ines Pires Da Silva on a clinical and multi-omics predictive model of resistance to neoadjuvant anti-PD1 in melanoma
• Professor Jayesh Desai on phase I results of a novel oral KRAS G12D inhibitor in patients with advanced or metastatic solid tumors
• Dr Monica Tang on factors associated with increased distress and survivorship concerns in Australian cancer survivors.