The European Society for Medical Oncology (ESMO) Congress 2024 took place in Barcelona, Spain, 13-17 September 2024, and featured some significant breakthroughs in cancer drug discovery.

NIAGARA Phase III trial

AstraZeneca presented positive results from its NIAGARA Phase III trial, a global study to evaluate the first perioperative immunotherapy regimen in muscle invasive bladder cancer.

The NIAGARA results showed that treatment with Imfinzi (durvalumab) before and after surgery in combination with neoadjuvant chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS).

There was also a meaningful improvement in the key secondary endpoint of overall survival (OS) versus neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC).

Results from the key secondary endpoint of OS showed the Imfinzi-based regimen reduced the risk of death by 25% versus neoadjuvant chemotherapy.

An estimated 82.2% of patients treated with Imfinzi were alive at two years compared to 75.2% with neoadjuvant chemotherapy.

SunRISe-4 Phase II trial

Janssen-Cilag revealed interim data from the ongoing Phase II SunRISe-4 study showing neoadjuvant treatment with investigational TAR-200 plus cetrelimab (CET) achieved nearly double the pathological complete response (pCR) rate compared to CET alone in patients with muscle-invasive bladder cancer (MIBC) who are ineligible or refuse neoadjuvant platinum-based chemotherapy and are scheduled for radical cystectomy (RC).

In the interim analysis of the SunRISe-4 study, the centrally confirmed pathologic complete response (pCR, [T0]) rate was 42% with neoadjuvant TAR-200 plus CET compared to 23% with CET alone in patients with histologically proven, non-metastatic MIBC.

The pathological overall response (pOR) rate (defined as the proportion of patients ≤pT1) was 60% compared to 36%, respectively.

NATALEE Phase III trial

Novartis shared an updated analysis from the pivotal Phase III NATALEE trial, investigational Kisqali (ribociclib) added to endocrine therapy (ET)

The results show a deepening benefit beyond the three-year treatment period, reducing the risk of recurrence by 28.5% compared to ET alone, in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC).

The company reported that invasive disease-free survival benefit continued to increase after completion of the three-year treatment period across all patient subgroups, including those with node-negative disease.

The results remained consistent across secondary endpoints, including distant disease-free survival, with a trend for improved overall survival.

HIMALAYA Phase III trial

AstraZeneca also announced five-year overall survival data from the HIMALAYA Phase III trial in patients with unresectable hepatocellular carcinoma (HCC) who had not received prior systemic therapy and were not eligible for localised treatment.

The results showed that Imfinzi (durvalumab) plus Imjudo (tremelimumab-actl) demonstrated sustained overall survival benefit in advanced liver cancer with one in five patients alive at five years.

At five years of follow-up, this latest exploratory analysis showed that a single priming dose of Imjudo added to Imfinzi, called the STRIDE regimen (Single Tremelimumab-actl Regular Interval Durvalumab), reduced the risk of death by 24% compared to sorafenib.

An estimated 19.6% of patients treated with the STRIDE regimen were alive at five years versus 9.4% for those treated with sorafenib.

In a subgroup analysis of patients in the trial who achieved disease control, defined as complete or partial response or stable disease, 28.7% of those treated with the STRIDE regimen were alive at five years versus 12.7% of patients treated with sorafenib.

An exploratory analysis of depth-of-response (DpR) showed that more patients treated with the STRIDE regimen experienced deep responses leading to longer survival compared to sorafenib.

MARIPOSA-2 Phase III trial

Johnson & Johnson announced updated results from the Phase III MARIPOSA-2 study, which showed Rybrevant (amivantamab) combined with chemotherapy led to a favourable trend toward improved OS compared to chemotherapy alone.

At the second interim analysis for the MARIPOSA-2 clinical trial, with a median follow-up of 18.1 months, 50% of patients treated with amivantamab plus chemotherapy were still alive at the 18-month landmark, compared to 40% of those receiving chemotherapy alone.

Amivantamab plus chemotherapy showed a significant improvement in treatment discontinuation rates (22%), with nearly five times as many patients remaining on therapy at 18 months compared to chemotherapy (4%).

Additionally, patients treated with amivantamab plus chemotherapy experienced a 27% reduction in the risk of symptomatic progression.

The time to subsequent therapy was prolonged with the amivantamab plus chemotherapy combination compared to chemotherapy (median time to subsequent therapy, 12.2 vs 6.6 months, respectively), which also reduced the risk of second disease progression or death by 39%.

Phase I study of givastomig

I-Mab presented encouraging top-line results from its ongoing Phase I clinical study of givastomig, a novel first-in-class/ Claudin18.2 (CLDN18.2) and 4-1BB bispecific antibody immunostimulant, in patients with advanced cancers, especially gastric cancers (including gastroesophageal carcinoma, or GEC).

Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin 18.2-positive tumour cells that conditionally activates T cells via the 4-1BB pathway in the tumour microenvironment, where Claudin 18.2 is expressed.

Of the 43 patients with CLDN18.2+ GEC who received givastomig monotherapy at doses ranging from 5 to 18mg/kg, partial responses were observed in seven patients (one at 5mg/kg, one at 8mg/kg, four at 12mg/kg, and one at 18mg/kg) with an objective response rate (ORR) of 16.3% (7/43 patients) for single agent givastomig.

Five of the seven patients who had achieved a partial response (71%) had previously received a checkpoint inhibitor. Stable disease (SD) was reported in 14 patients, which resulted in a disease control rate (DCR) of 48.8% (21/43 patients).

Interim data for mRNA vaccine

WestGene Biopharma shared the latest clinical data for its EBV-positive tumour mRNA vaccine, WGc-043.

According to the company, WGc-043 demonstrated exceptional safety, immunogenicity, and anti-tumour activity in the latest clinical trials.

The vaccine is being developed specifically for adult patients with advanced EBV-positive solid tumours and refractory or relapsed EBV-positive lymphomas, diseases for which there are currently no effective, low-toxicity treatment options.

Interim clinical data highlighted the vaccine’s ability to activate the patient’s immune system, leading to the production of cytotoxic T cells, antigen-specific antibodies and memory T cells that target and destroy cancer cells.

This mechanism could offer a promising alternative to conventional CAR-T and monoclonal antibody therapies and also aims to prevent tumour recurrence, particularly for patients with late-stage nasopharyngeal carcinoma and NK/T cell lymphoma.

Clinical data in melanoma

Linnaeus Therapeutics announced clinical data from its dose-expansion cohort of LNS8801 as a monotherapy in patients with metastatic cutaneous melanoma who could not tolerate immunotherapy due to prior immune-related adverse events.

LNS8801 given alone was tolerable without unanticipated toxicities and demonstrated encouraging antitumour activity in patients with metastatic cutaneous melanoma who had prior severe immune-related adverse events on immune checkpoint inhibitor therapies.

LNS8801 monotherapy treatment resulted in a disease control rate of 100% in biomarker-positive patients, with a preliminary progression-free survival of over six months.

This included a patient that has been on treatment for over 4.5 years with resolution of all soft-tissue lesions and no evidence of active disease in the residual bone-associated target lesion or elsewhere.

TiNivo-2 Phase III trial

AVEO Oncology shared the TiNivo-2 Phase III clinical trial results in patients with advanced metastatic renal cell carcinoma (RCC) whose tumours had progressed following prior ICI treatment.

The TiNivo-2 clinical trial was designed to evaluate the treatment of Fotivda, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), in combination with nivolumab, a PD-1 inhibitor, versus Fotivda as a single agent therapy to investigate the benefit of ICI challenge in a relapsed refractory setting.

In the study, the addition of nivolumab to Fotivda (0.89mg) following prior immunotherapy did not enhance efficacy over Fotivda (1.34mg) alone, so the study did not meet its primary endpoint.

In pre-planned analyses of the Fotivda control arm, a 9.2 month median PFS was observed for patients that received Fotivda monotherapy as second line and for patients immediately following ICI combination therapy.

The experimental arm (nivolumab plus tivozanib) had a 7.3 month median PFS in the second line and a 7.4 month median PFS for patients immediately following ICI combination therapy.

Diana Spencer, Senior Digital Content Editor, DDW