The ESMO 2024 conference will unveil significant new findings in gastrointestinal cancers, highlighting advancements in the treatment of cervical, endometrial, and ovarian cancers.

The treatment landscape for ovarian and endometrial cancers is evolving swiftly, with exciting data readouts of several novel targets. MorphoSys will present data from its Phase II trial of the EZH2/EZH1 inhibitor, tulmimetostat, targeting ARID1A-mutated ovarian clear cell carcinoma. Acrivon Therapeutics will showcase its Phase II dual CHK1/2 inhibitor’s response, ACR-368 for ovarian and endometrial cancers. At the same time, NextCure will reveal early results from its Phase I/II trial of the LAIR-1 fusion protein, NC410, in ovarian cancer. Eisai’s Phase I CBP/β-catenin inhibitor, E7386’s data expected in advanced endometrial cancer, and Immunocore will present its Phase I PRAME × CD3 ImmTAC T cell engager, brenetafusp, for platinum-resistant ovarian cancer.

In the realm of antibody-drug conjugates (ADCs) for treating ovarian cancer, Profound Bio, Sutro Biopharma, and Abbvie/ImmunoGen will present data on their FRα-targeting ADCs, including Rinatabart Sesutecan, Luveltamab tazevibulin, and Mirvetuximab Soravtansine, respectively. Additionally, Gilead’s and AstraZeneca’s TROP-2 ADCs, TRODELVY and DatoDxd, respectively, will be featured for their roles in treating endometrial and ovarian cancers.

Within cervical cancer, Merck will present eagerly awaited results from its Phase III KEYNOTE-A18 study, based on which KEYTRUDA has recently received FDA approval for use with chemoradiotherapy in FIGO 2014 Stage III-IVA cervical cancer. Additionally, Merck will also highlight data on its investigational TROP-2 ADC, Sacituzumab Tirumotecan, for recurrent or metastatic cervical cancer.

Amid these successes, Merck encountered a setback with KEYTRUDA in newly diagnosed, high-risk endometrial cancer, with these disappointing results set to be presented as a late-breaking abstract at the conference. In the queue for trial failures, another late-breaking abstract showcasing results from Phase III ATHENA-COMBO, comparing rucaparib with BMS’s nivolumab combination therapy for newly diagnosed ovarian cancer. 

Unveiling the latest in Gastrointestinal Cancers treatment landscape

• Abstract Number – LBA 28
• Abstract Type – Proffered Paper session
• Indication - Newly Diagnosed Endometrial Cancer

Title: KEYTRUDA Faces Setback in Newly Diagnosed Endometrial Cancer. What’s Next for Merck in this therapeutic space?

Executive Summary: Despite KEYTRUDA's strong performance in various endometrial cancer settings, Merck's recent attempt to position it as a post-surgery therapy for newly diagnosed patients has fallen short as demonstrated in the Phase III KEYNOTE-B21 study.

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Merck’s anti-PD-1 therapy, KEYTRUDA, has three approved uses in the US for treating endometrial cancer. First, in combination with LENVIMA (lenvatinib) for patients with pMMR or non-MSI-H advanced endometrial carcinoma who have progressed after prior treatments, based on KEYNOTE-775. Second, as a monotherapy for patients with MSI-H or dMMR advanced endometrial cancer, following progression on previous therapies, based on KEYNOTE-158. Lastly, the most recent approval, based on KEYNOTE-868, for use with carboplatin and paclitaxel in primary advanced or recurrent endometrial carcinoma.

While KEYTRUDA already boasts a pair of approvals to treat certain forms of endometrial cancer, a recent effort to prove the PD-1 inhibitor’s worth as a post-surgery add-on therapy in newly diagnosed patients has fallen short. In May 2024, Merck provided an update on its KEYNOTE-B21 study, investigating pembrolizumab in combination with adjuvant chemotherapy (with or without radiotherapy) for patients with newly diagnosed high-risk endometrial cancer, which did not meet its primary endpoint of disease-free survival (DFS). A full evaluation of the data from this study is ongoing, and the company will be presenting these results at the ESMO 2024 conference. 

Over the past year, Merck’s KEYTRUDA has faced fierce competition from GSK’s JEMPERLI as both companies vie for dominance in endometrial cancer treatment. In early 2023, JEMPERLI snagged a historic win as the first immunotherapy approved for first-line endometrial cancer. Shortly after, KEYTRUDA, in combination with standard chemotherapy, demonstrated superior results in preventing tumor progression or death in advanced or recurrent disease compared to chemotherapy alone. At the Society of Gynecologic Oncology 2023 meeting, both GSK and Merck showcased detailed data from their respective trials. KEYTRUDA showed promising results in MMR proficient (pMMR) patients, giving it an edge over JEMPERLI in this critical subgroup. However, GSK was the first to secure FDA approval for JEMPERLI in newly diagnosed patients with dMMR or MSI-H tumors, gaining a significant foothold in this niche in July 2023. Despite KEYTRUDA topping pharmaceutical sales charts in 2023, the drug has experienced a series of clinical ups and downs in 2024. 

• Abstract Number – 758P
• Abstract Type – Poster
• Indication – Ovarian Cancer

Title:  NextCure’s NC410’s Clinical Potential in Ovarian Cancer Gains Momentum with Emerging Phase Ib Data 

Executive Summary: NextCure’s NC410, a first-in-class LAIR-2 fusion protein, in combination with pembrolizumab demonstrates early promise in ovarian cancer, with encouraging Phase Ib results and further data expected at ESMO 2024.

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NextCure is committed to discovering and developing novel, first-in-class, and best-in-class therapies to treat cancer, among which is NC410. It is a first-in-class immunomedicine designed to block immune suppression mediated by LAIR-1, an immunomodulatory receptor expressed on a variety of immune cells including T cells and myeloid cells. The drug is currently being evaluated in a Phase I/II trial in combination with pembrolizumab for the treatment of ovarian cancer. 

The company presented Phase Ib data from this trial at the ASCO 2024 in a poster presentation in immune checkpoint inhibitor (ICI) naïve and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer. While MSS/MSI-L CRC and ovarian cancer are difficult to treat and recalcitrant to immunotherapy, the combination demonstrated clinical activity against both tumor types. It resulted in partial responses and stable disease in both CRC and ovarian cancer. While the focus of that presentation was on the targeted CRC patient population, the company is geared up to report the results from the ongoing ovarian cancer cohort expansion at the ESMO 2024. In June 2024, NextCure completed enrollment of an additional 16 ovarian cancer patients among the 100 mg and 200 mg cohorts of the Phase Ib portion of this Phase Ib/II study of NC410. 

Top 10 Key Abstracts for Gynecologic Cancer