Turning high unmet need into meaningful progress – advancing ADC strategies in rare and difficult-to-treat cancers

In oncology, some of the most pressing unmet needs lie not in the most common tumour types but in cancers that are rare, aggressive or historically underserved.

For organisations committed to transforming outcomes, solving difficult-to-treat cancers is both a moral imperative and a scientific opportunity.

Antibody-drug conjugate (ADC) platforms are central to that mission, bringing together deep expertise and innovative technology.

Across many cancers, survival remains poor, therapeutic options are limited and the urgency for new approaches is high.

In my role, I see firsthand the progress being made in the treatment of advanced solid tumours, yet patients still face limited options and significant unmet needs. This reality motivates us to think boldly and act with urgency.

In response, multiple modalities are being pursued to help redefine the standard of care, recognising the many challenges cancer patients face today.

Among these modalities, ADCs allow us to harness the precision of antibody targeting and pair it with the potency of cytotoxic payloads – creating the possibility of delivering what we describe as ‘today’s insights into tomorrow’s breakthroughs’.

This targeted approach aims to elevate the standard of care and maximise clinical benefit while helping to mitigate the impact of traditional therapies.

One investigational ADC, ABBV-706, is directed against SEZ6, a transmembrane protein highly expressed in neuroendocrine lineage tumours such as small cell lung cancer (SCLC).

Early clinical data is encouraging. In patients with relapsed or refractory SCLC, durable responses and a manageable safety profile have been observed.

What makes this especially meaningful is that responses were seen across key subgroups, including those with brain metastases and platinum-refractory disease – areas where therapeutic options are limited and unmet need is significant.

Beyond SCLC, ABBV-706 has demonstrated notable response rates in other rare neuroendocrine tumours compared with traditional chemotherapies.

These results underscore the intent to move beyond incremental improvement and achieve meaningful change in patient outcomes.

In addition to these novel assets, a suite of ADCs in solid tumours is advancing, including a cMet-targeted ADC, ABBV-400, which has shown promise across a range of difficult-to-treat cancers.

Beyond solid tumours, there is also a commitment to advancing novel ADCs in rare haematologic cancers such as blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Pivekimab sunirine (PVEK) is a CD123-targeting ADC developed for BPDCN and other CD123-positive haematologic malignancies. A Biologics License Application has recently been submitted to the US FDA for PVEK in BPDCN based on data from a global phase 1/2 study presented in 2025.

PVEK has also been granted Breakthrough Therapy designation in this indication by the US FDA, further emphasising the unmet need in BPDCN.

The depth and diversity of the ADC portfolio is intentional.

At ASCO 2025, the breadth of this approach was highlighted, spanning both solid tumours and blood cancers and demonstrating the strategic reach of ongoing R&D efforts.

As part of that strategy, three key solid tumour areas are prioritised: gastrointestinal (with an emphasis on colorectal); gynaecologic (notably ovarian) and lung cancers; alongside haematologic malignancies.

The development paradigm emphasises being biomarker-driven, patient-centric and ambitious.

This includes exploring therapies in tumour types where traditional chemotherapy has had limited success and where even modest improvements may translate into major clinical impact.

Through various mechanisms, the goal is to create targeted medicines that either impede the reproduction of cancer cells or enable their elimination, ultimately replacing chemotherapy.

Rare cancers and those resistant to standard therapies, such as certain haematologic malignancies and solid tumours, pose unique challenges due to their complex biology and limited patient populations.

The ADC pipeline is designed to address these gaps by:

• Identifying actionable, tumour-specific markers that can be used to target rare cancers
• Developing next-generation linkers with improved stability and potent payloads suited to specific cancer types
• Incorporating biomarker-driven patient selection strategies to ensure and amplify clinical benefit
• Exploring novel combination approaches to overcome complex barriers, including the recent licensing of a PD-1/VEGF bispecific antibody with the intent to investigate combinations with Temab-A.

For patients diagnosed with SCLC, BPDCN or other rare, difficult-to-treat cancers, the path ahead has too often been marked by limited options and challenging prognoses.
The ambition is to change that narrative.

With ABBV-706, PVEK and an expanding ADC portfolio, the goal is to move towards a future in which patients receive more potent, precisely targeted therapies earlier in their treatment journey.

Through ongoing translational research, early clinical trials and collaborations with partners and patient communities, insights are continually being gathered to refine ADC design and optimise efficacy while minimising side effects.

Although many steps remain to bring these innovative treatments forward – including pivotal trials, regulatory review and eventual real-world access – the early signs are clear.

Progress is being made. And for patients and clinicians alike, that progress matters.

Daejin Abidoye is Therapeutic area head, oncology, solid tumour and haematology at AbbVie