News from AACR 2024: Tuesday’s highlights

San Diego

Today, National Cancer Institute leaders discussed cancer breakthroughs and the importance of securing support from lawmakers for the NCI and National Institutes of Health in the session ‘The Cancer Moonshot: Opportunities to Fulfill the Vision of the National Cancer Plan – Dedicated to the Memory of Sen. Dianne Feinstein’.

Major symposia and mini-symposia featured a wide variety of scientific topics, including ‘Molecular Glues, PROTACs, and Next-Gen Degraders: Discovery and Early Preclinical Advances’, which showcased preclinical advances for new oncology targets and their respective indications, and ‘Discovering and Broadening the Therapeutic Modalities of Immune Therapy’, which looked at mechanisms that contribute to the success of immune therapies and methods under investigation that broaden development.

Poster highlights

NeoImmuneTech presented a poster on a pre-clinical study that explored the efficacy of NT-I7 (efineptakin alfa) in combination with FOLFOX (a combination of 5-fluorouracil, leucovorin, and oxaliplatin), a first-line standard of care (SoC) for colorectal cancer, in an animal model of colorectal cancer (MC38, C57BL/6 mice). The study’s findings suggest a significant improvement in treatment outcomes when NT-I7 is used alongside FOLFOX, demonstrating a 69% reduction in tumour size compared to the administration of FOLFOX alone. While the overall Absolute Lymphocyte Count (ALC) in the blood was reduced by FOLFOX treatment, the number of anti-cancer specific T cells in the tumour was significantly increased in the combination group compared to FOLFOX alone.

GenFleet Therapeutics announced the latest findings for GFH547, an oral panRAS (ON) inhibitor, in a late-breaking research abstract. GFH547 is developed with novel mechanism of action by reshaping and repurposing intracellular cyclophilin A (CypA) protein to target active RAS proteins across most wild/mutant subtypes. Pre-clinical data demonstrated profound panRAS inhibitory activity of GFH547 and it holds the potential to overcome adaptive and acquired resistance against SIIP (switch II pocket)-based KRAS inhibitors.

Flare Therapeutics shared data identifying immunosuppressive cell phenotypes associated with high PPARG expression in urothelial cancer (UC) patients treated with anti-PD1 therapy. Flare scientists showed that circulating classical monocytes harbouring high levels of PPARG expression exhibited an immunosuppressive phenotype in UC patients who received anti-PD1 therapy. Findings corroborate molecular real-world data presented at the SITC 2023 Annual Meeting that demonstrated high PPARG expression in patients with muscle-invasive UC is associated with an immunosuppressive tumour microenvironment and shorter real-world progression-free survival to anti-PD1 treatment.

Alphamab Oncology announced data from a Phase I clinical study of anti-HER2 bispecific antibody-drug conjugate (ADC) JSKN003 for the treatment of HER2-expressing advanced solid tumours. As of the cut-off date March 15, 2024, the objective response rate (ORR) and disease control rate (DCR) was 56.3% and 90.6%, respectively. The ORR in patients with IHC 1+, 2+ and 3+ was 66.7% (6/9), 37.5% (6/16), and 85.7% (6/7), respectively. As for the efficacy of the HER2+ BC and HER2-low BC, the ORR was 100% (5/5) and 50.0% (5/10), respectively. JSKN003 demonstrated encouraging preliminary antitumor activity and exhibited a favourable tolerability and safety profile with low occurrence of haemotoxicity and ILD.

TILT Biotherapeutics presented promising preliminary safety and efficacy data from an ongoing Phase I clinical trial in platinum resistant or refractory ovarian cancer patients. TILT-123, an oncolytic adenovirus armed with tumour necrosis factor alpha (TNFα) and interleukin-2 (IL-2), in combination with MSD’s anti-PD-1 therapy Keytruda (pembrolizumab) was safe and demonstrated signs of efficacy in both platinum resistant and refractory ovarian cancer patients. Notably, disease control was seen in 71% of evaluable patients including one long lasting partial response in a patient with mucinous carcinoma. Tumour size reductions and significant immunomodulation were seen in injected and non-injected tumours, indicating the potential for a systemic response.

Ariceum Therapeutics demonstrated its new findings on the discovery of novel macrocyclic peptide radioligands for tumour therapy by mRNA display in collaboration with research partner, UCB. They described the selection and initial characterisation of macrocyclic peptides against an undisclosed target discovered using UCB’s mRNA-display technology platform, ExtremeDiversity. Macrocyclic peptides are potent ligands for radioligand therapeutics (RLT) that aim to selectively deliver radioisotopes to cancer tissues to eradicate tumour cells while limiting the damage to surrounding tissues.

Diana Spencer, Senior Digital Content Editor, DDW

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