Exploring what’s next in Phase I and Antibody-Drug Conjugates

Icon Writers / 27 May, 2024

Medical Oncologist and Icon’s Medical Oncology Research Committee Chair, A/Prof Jim Coward shares his insights on the future of cancer treatment, focusing on the promising developments in Phase I trials and how Antibody-Drug Conjugates (ADCs) are forging new hope for more cancer patients.

Exploring ADCs

ADCs are a relatively old concept but in recent years, researchers and oncologists are learning more about the benefits of ADCs and how they can be used to treat a wider range of tumours and cancer types. Currently, ADCs are commonly used in Phase I cancer clinical trials and have recently seen a significant increase in new ADCs being studied in a Phase I setting.

A/Prof Coward who leads Icon’s Phase I unit in Queensland, Australia explains the strength of these targeted therapies.

“An ADC is essentially two for the price of one – you’re getting chemotherapy which is linked to an antibody which is focusing on targeting a protein or receptor which is integral to a cancer’s aggressive behaviour, hence a very targeted approach,” said A/Prof Coward.

“We’re currently seeing some really promising results in patients with chemo-resistant disease and in diseases which are resistant to immunotherapies and other novel targeted therapies.”

Overcoming Resistance to Immunotherapy

A/Prof Coward also highlighted the ongoing efforts to overcome resistance to immunotherapy.

“We’re looking at using really novel combinations of already pre-existing chemotherapy agents targeting smaller immune mediators responsible for resistance to those immunotherapies.”

ADCs are administered intravenously and are gaining significant traction in the treatment of gynaecological cancers, particularly breast and ovarian. “In the past 20 years, breast cancer patients with high levels of HER2+ have been treated with targeted drugs like Herceptin and Perjeta,” explained A/Prof Coward.

“However, those with lower HER2 levels weren’t eligible for such treatments until recently – now, new therapies are available that use antibody-drug conjugates for tumours which don’t necessarily over express HER2+.

“These therapies, which link an antibody to HER2+ with chemotherapy, have shown impressive results, not only resistant to chemotherapy but also resistant to prior HER2 directed therapies.

Similarly, in ovarian cancer, particularly in cases resistant to chemotherapy, favourable results have been seen with antibodies targeting proteins linked to chemotherapy resistance.

Implications for Current and Future Patients

Discussing the implications for current and future patients, A/Prof Coward is optimistic. “In ovarian cancer alone, there are more than 15 ADCs currently under preclinical investigation, some with really positive preliminary results,” he explained.

“It means that we’re really forging new horizons for patients who previously would have been transferred to palliative care because there were no other suitable treatment options. We’re seeing incredible survival benefits in patients who otherwise wouldn’t have had no other systemic treatment available.”

Looking Ahead

ADCs, immunotherapy, and fibroblast growth factor receptors (FGFR) inhibitors are some of the most promising treatments for cancers.

“Patients with certain mutations, for example FGFR mutation will often have very aggressive disease and exhibit early resistance to chemotherapy, however targeted therapies are resulting in positive results and prolonged survival rates.”

“However, some of them can have severe side effects, so managing these while maintaining the treatment’s effectiveness is proving to be our current challenge.

“Overall ADCs and agents targeting immuno-resistant pathways and targeted therapies for specific gene mutations are really encouraging for future outcomes, and that’s why I focus on incorporating trials in my practice – to learn more and help extend people lives.”

For more information on Research at Icon. View our Annual Research Reports.

Phase I trials at Icon

Icon is proud to operate Australia’s largest private Phase I clinical trials program and leads the way in first in-human trials helping to evolve cancer treatments. Phase I makes up approximately 30% of Icon’s trial portfolio.

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