The next generation of cancer therapies revealed at AACR 2026

The American Association for Cancer Research (AACR) Annual Meeting 2026 took place 17-22 April 2026. Here we share some of the themes discussed and key data presented at the event.

Dominant themes

Allan Jordan, Vice President, Oncology Drug Discovery, Sygnature Discovery, shared his key take-homes messages from the event:

• The cancer research landscape is facing strong headwinds in the face of global uncertainty and turmoil. Whilst Congress overturned a budget that would have seen cancer research funding cut by over 40% and instead provided a modest increase, the future funding landscape remains uncertain and fragile. VC funding remains scarce and many promising projects and expert teams are being abandoned due to lack of funding. Cancer research is a long-term endeavour fraught with uncertainties of its own, and funding challenges now will cause damaging ripples for many years to come, stifling much needed progress and shrinking the collective expertise of the cancer research community as experts, students and early career researchers abandon the filed for a less uncertain future.
• We finally seem to be moving beyond the term “undruggable”, with many new disclosures of therapeutics engaging with complex target classes such as transcription factors, disordered proteins, closely related paralogues and ternary complexes including not just proteins but protein-RNA and protein-DNA interfaces.
• Induced proximity therapeutics remain a significant area of focus, but we see a marked shift from heterobifunctional molecules toward molecular glues.
• ADCs remain buoyant, but still largely coalesce around just three payload classes, though this is starting to change, with the emergence of enthusiasm for more adventurous payloads designed to exploit tumour-specific processes and drug targets.
• AI in drug discovery also remains the topic of any presentations and conversations, and implementation of AI is now prevalent across the whole spectrum of cancer research. But the path forwards to better utilisation and the best places to deploy AI in cancer discovery still remains a subject of intense debate.

Nested reports encouraging clinical activity for its Pan-RAF/MEK molecular glue

Nested Therapeutics reported initial clinical results from its ongoing Phase I study evaluating NST-628, a brain-penetrant non-degrading pan-RAF/MEK molecular glue, in patients with advanced solid tumours.

The data presented demonstrate encouraging single-agent anti-tumour activity and a favourable tolerability profile in a range of RAF and RAS-mutant tumours. These included a 38% response rate and 85% disease control rate at the recommended dose in heavily pretreated NRAS and BRAF Class II/III melanoma.

Darrin Miles, Chief Executive Officer of Nested Therapeutics, said: “We are particularly encouraged by the durable responses in NRAS and BRAF Class II/III melanoma – large patient populations with historically poorer outcomes and for whom there are no approved targeted therapy options – as well as early signals of clinical activity beyond melanoma, including in KRAS-mutant solid tumours and evidence of brain penetrance.”

Responses to NST-628 were observed across multiple tumour types and genotypes, including KRAS-mutant ovarian and cervical cancers – highlighted by an ongoing partial response in a KRAS G12V-mutant cervical cancer patient with a treatment duration exceeding one year – as well as NRAS/BRAF Class III-mutant colorectal cancer and BRAF Class II-mutant thymic cancer.

Pheast shares Phase Ia data showing target engagement for PHST001

Pheast Therapeutics presented initial Phase Ia clinical data and new preclinical findings for PHST001, an IgG4 anti-CD24 macrophage checkpoint inhibitor.

“The data presented at AACR suggest that PHST001 may address a longstanding challenge in translating the therapeutic potential of macrophage biology into a cancer treatment with the right balance of activity and tolerability,” said Roy Maute, CEO and Co-founder of Pheast Therapeutics. “The preclinical data further support rationally designed therapeutic combinations informed by CD24 biology, reinforcing the breadth of PHST001’s development potential.”

In the ongoing Phase Ia first-in-human study, PHST001 was generally well-tolerated across dose-escalation cohorts. Most treatment-related adverse events were Grade 1 or 2.

The dataset demonstrated linear pharmacokinetics, increasing CD24 receptor occupancy at higher dose levels, and pharmacodynamic changes consistent with innate immune activation. Early signs of clinical activity were observed, including disease stabilisation and tumour shrinkage.

In preclinical studies including patient-derived tumour xenograft models, PHST001 enhanced macrophage-mediated tumour control and prolonged survival in combination with chemotherapies and antibody-drug conjugates. PHST001 also inhibited metastatic spread and reduced metastatic burden across multiple in vivo models.

Clasp Therapeutics unveils first-in-class KRas T cell engager CLSP-5282

Clasp Therapeutics presented preclinical data on CLSP‑5282, a TCE targeting KRas G12V − one of the most prevalent oncogenic driver mutations in solid tumours.

Clasp’s platform leverages peptide-HLA presentation to expose intracellular mutant proteins to the immune system, enabling TCEs to target oncogenic drivers inaccessible to conventional antibody approaches.

CLSP-5282 targets the KRas G12V peptide presented by HLA-A*03:01, redirecting T cells to eliminate tumour cells harbouring this mutation. This mutation-HLA pairing defines a substantial, well-characterised patient population and provides the foundation for a scalable pipeline of KRas TCEs targeting additional mutation–HLA combinations already validated in translational and clinical studies.

“KRas inhibitors have proven the target is druggable − but resistance is universal,” said Vipin Suri, Chief Scientific Officer of Clasp Therapeutics. “Intriguingly, resistance mechanisms including KRas amplification and enhanced antigen presentation are likely to increase tumour sensitivity to TCEs such as CLSP-5282. This creates a compelling opportunity for CLSP-5282 both after inhibitor progression and in rational combination strategies targeting KRas through complementary, orthogonal mechanisms.”

Nuvalent presents clinical and preclinical data for zidesamtinib

Nuvalent announced new clinical and preclinical data for zidesamtinib, an investigational ROS1-selective inhibitor.

James Porter, Chief Executive Officer at Nuvalent, said: “We’re highly encouraged by these clinical data for patients previously treated with repotrectinib or taletrectinib in our ARROS-1 trial, which we believe further reinforce the medical needs that remain for patients with ROS1-positive NSCLC despite the availability of new treatment options.”

Zidesamtinib is being evaluated in ARROS-1, a Phase I/II clinical trial in patients with advanced ROS1-positive NSCLC and other solid tumours. The clinical data presented are from a subgroup of patients with advanced ROS1-positive NSCLC in ARROS-1 who had been previously treated with the dual TRK/ROS1 TKIs repotrectinib and/or taletrectinib.

Treatment with zidesamtinib resulted in clinically meaningful activity in this population, including in patients with the ROS1 G2032R resistance mutation and those with CNS disease.

Preclinical data were presented from analyses of the brain penetrance and intracranial ROS1 G2032R antitumor activity of zidesamtinib compared to the dual TRK/ROS1 inhibitors repotrectinib and taletrectinib.

Zidesamtinib demonstrated the highest cell permeability in MDCK-MDR1 cell lines and highest brain-to-plasma partitioning in rats, as well as the most sustained intracranial efficacy in a mouse ROS1 G2032R brain tumour model, with all mice surviving to study end.

NEOK Bio showcases promising pre-clinical data

Oncology therapeutics NEOK Bio showcased two poster presentations at AACR highlighting its ADC pipeline.

The presentations detailed NEOK’s emerging pipeline of next-generation ADCs engineered to target proteins broadly expressed across tumour types with high unmet need. Included were preclinical data findings for its two lead bispecific candidates – NEOK001 and NEOK002, both of which are utilising NEOK002 linker-payload technology.

Data for NE0K001 show that the bispecific ADC demonstrated enhanced efficacy and promising tolerability. Among the data presented, other details included:

• Potent dual target cytotoxicity and strong bystander killing, supporting activity in heterogeneous solid tumours
• Broad efficacy across 38 PDX models, achieving 84% tumour growth inhibition and 53% deep tumour regression across nine major cancer types
• Outperformed clinical benchmark ADCs, including I Dxd and zilovertamab vedotin, and successfully regressed I Dxd-treated regrowing tumours
• Observed favourable safety profile in GLP toxicology studies (HNSTD: 60 mg/kg) with stable DAR and predictable pharmacokinetics

Data for NEOK002 showed promising anti-tumour activity and an enhanced therapeutic window. Among the data presented, other details included:

• Dual-targeting design enhances binding and internalization in dual-positive tumour cells while reducing off tumour EGFR engagement
• Robust antitumor activity across 36 PDX models, achieving tumour regressions in 78%, including KRAS mutant and heavily pretreated tumours
• Favourable safety profile with minimal impact on keratinocyte proliferation and reduced inhibition of EGFR signalling versus cetuximab-based ADCs
• Strong combination potential sotorasib, enabling extended tumour regression for 58 days in KRAS G12C-mutant models

Both programmes have received Investigational New Drug (IND) approval from the US Food and Drug Administration (FDA), and NEOK plans to initiate Phase I clinical trials in 2Q 2026, with initial clinical data readouts anticipated in 2027.

“These preclinical findings underscore the potential of our next-generation ADC pipeline to overcome the limitations of conventional monovalent designs,” said Mayank Gandhi, CEO of NEOK Bio. “As we prepare to accelerate both candidates into clinical development, we look forward to sharing their differentiated mechanisms and compelling pre-clinical activity at ACCR 2026.”

Immatics data shows promising PRAME approach in cancer

Biotech company Immatics presented a patient case abstract at AACR. The presentation highlighted the case of a 17-year-old adolescent with PRAME-positive advanced nephroblastoma, a malignant kidney cancer that predominantly occurs in children. The abstract showed the patient being treated with a PRAME-directed cell therapy using Immatics’ PRAME T-cell receptor (TCR). This therapeutic approach was used after all other available treatments had been exhausted.

Following treatment, the patient experienced a deep anti-tumour response, with remission observed three months post-infusion and ongoing at six months of follow-up. PET scan and MRI imaging demonstrated marked tumour regression across all lesion sites. Additionally, liquid biopsy monitoring showed no more tumour-derived DNA, indicating molecular remission.

“We are very grateful to Immatics for providing the PRAME-directed TCR that enabled us to reprogram the paediatric patient’s cells. We hope that possible further clinical evaluation may demonstrate the potential of PRAME-targeted cellular immunotherapies in helping other children and adolescents with cancer, as seen in this patient,” said Christian Seitz, treating physician and Group Leader of the Translational Immunotherapy group at KiTZ, German Cancer Research Center (DKFZ) and Heidelberg University Hospital (UKHD).

Cedrik Britten, Chief Medical Officer at Immatics, added: “Seeing such a profound response in a paediatric patient who had no treatment options left is both remarkable and deeply encouraging for everyone dedicated to making a meaningful impact on the lives of patients with cancer. It reinforces our belief in PRAME as a powerful target and highlights the potential of cell therapy for paediatric cancers, where tumours often show high PRAME expression. These results support continued evaluation of PRAME-directed cell therapies in paediatric cancers while exploring new therapeutic options for children facing such devastating diseases.”

Amphista discloses protein degrader candidate

Amphista Therapeutics disclosed the chemical structure of its lead Targeted Glue protein degrader AMX-883 at AACR.

The company gave an oral presentation of its candidate during the New Drugs on the Horizon session. It detailed the discovery and optimisation of a series of DCAF16-recruiting BRD9 degraders which yielded AMX-883. The DCAF16-dependent mechanism of action of AMX-883 was structurally confirmed by high-resolution cryo-EM of the ternary complex, revealing true glue-like interactions that stabilise the complex.

Amphista nominated AMX-883 as its first clinical development candidate in October 2025, based on a preclinical data package which expands the growing evidence base defining a critical role for BRD9 in maintaining acute myeloid leukaemia (AML) blast stemness and survival.

The data showcased that by degrading BRD9, AMX-883 relieves the differentiation block characteristic of AML, inducing expression of myeloid differentiation genes and repressing pro-proliferative programmes.

Critically, through BRD9 degradation, AMX-883 blocks patient-derived tumour growth in vivo as a monotherapy and demonstrated synergistic efficacy while in combination with venetoclax and prevented the emergence of resistance to venetoclax in vitro, addressing a major clinical challenge in AML.

Martin Pass, Chief Development Officer at Amphista Therapeutics, said: “I’m delighted to be able to share the preclinical characterisation data for AMX-883, our BRD9 Targeted Glue degrader, for the first time at AACR. Not only does it showcase the ability of our Eclipsys platform to deliver truly differentiated and high-quality molecules, but it also brings new insight and mechanistic understanding to BRD9’s role in AML and the hope that targeted removal from AML blasts may bring profound benefit to patients.”

Patrick Kelly, Chief Medical Officer at Amphista Therapeutics, added: “AML is a devastating disease with a poor prognosis, and most patients will relapse or become refractory to current treatments within a matter of months. As a karyotype-independent, pro-differentiation agent, AMX-883 has the potential to address a critical unmet need in AML by offering a broadly applicable treatment option. We are excited to advance this highly differentiated molecule into clinical trials in the second half of this year bringing new hope to patients facing this serious disease.”

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