Connecting Health Equity to Clinical Trial Access: A Conversation With AstraZeneca’s Carlos Doti, MD

As vice president of medical affairs for AstraZeneca’s US Oncology Business Unit, Carlos Doti, MD, develops the medical strategy across the pharmaceutical company’s oncology portfolio, which in 2022 had 7 FDA approvals across diseases and indications.¹

But approvals are not the end of the story, said Doti, who brings his experiences growing up in Buenos Aires, Argentina, to his role. In an

Doti

interview that took place during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in June, Doti shared how discovering new molecules and developing “the best medicines” is just one part of a broader strategy that is linked to health equity.

“It’s futile to bring more molecules into the market that can never reach the patient,” Doti said. He outlined what he called the pillars of his company’s research and development strategy.

Develop the best medicines. Doti said AstraZeneca’s strategy involves “therapies that will interact directly with the cancer,” including targeted therapies and antibody-drug conjugates. Another aspect, he said, is achieving breakthroughs in immunology so the immune system can “help” drugs in combinations eradicate cancer. A hematologist, Doti is particularly enthusiastic about the T-cell engager TNB-486, which AstraZeneca acquired in 2022.² Data presented at ASCO showed that TNB-486, a CD19 × CD3 bispecific antibody, had a 91% efficacy in a small group of patients with follicular lymphoma who previously had been treated with CD20-directed therapy.³

Fight cancer as early as possible. Innovations that allow detection and treatment of cancer as early as possible can transform care, Doti said. He referred to the overall survival results from the phase 3 ADAURA trial (NCT02511106), which were presented in ASCO’s plenary session and showed a 50% reduction in mortality when used in the adjuvant setting in early-stage EGFR-mutated lung cancer. Results showed 88% of the patients were still alive at 5 years.⁴ “That’s extraordinary,” Doti said. “But you can only do that if you intervene earlier.”

Find the patients who will benefit. This can involve using assays to screen for mutations, but it also means having systems for screening patients.

Biomarker-driven trials dominated the 20 major studies that AstraZeneca presented at ASCO 2023, including the readout of ADAURA results and late-breaking results from DESTINY-PanTumor02 (NCT04482309), which evaluated the efficacy of trastuzumab deruxtecan (Enhertu) across a range of HER2-positive cancers.⁵

Doti described the strategy of meeting unmet need as a worthwhile pursuit. “We can make a bigger difference if we go into unexplored areas,” he said. “It will take time. It will take some learning, because every time that you go to uncharted territory, you may hit some bumps. But we think that we can benefit more patients by going into spaces where no one has gone before—or, is it fair to say, [where] no one has data?”

As excited as he was about the ADAURA data, Doti said it’s possible to push the limits even more. “Can we find fingerprints in the DNA of patients at earlier stages, even before the tumor has grown or has been made visible? And in hematology, it’s a safe space to do that because the blood is more accessible; you don’t have to do a biopsy,” he said.

Access to Clinical Trials and Health Equity
Doti talked at some length about the need to bring clinical trials and testing to geographic areas where they are not accessible. He said his team is working on a project to close the gaps for those who live in areas that lack clinical trials and where access to medicines can take years following FDA approval. Doti said this is where growing up in Argentina informs his work.

“When I started my career in hematology [in Argentina] a long, long time ago, a clinical trial was the end of the line,” he said. “It was something that you did [in the] third line. Today, clinical guidance across the world puts clinical trials as soon as first line or second line. If you’re not making clinical trials available to [patients], or if the molecules are approved but patients cannot get them, are we not restricting the possibility of patients getting better care?”

Doti said the need to make clinical trials more accessible ties directly to his medical affairs role. It is essential for him to identify patients who are not represented in clinical trials and to find opportunities for these patients to participate in research. The way to address this, he said, is to identify the typical methods that pharmaceutical companies use to gather evidence and to find places for underrepresented patients to access one or more of those paths.

Doti said companies generate evidence in 3 ways: pivotal trials for a drug’s approval, real-world evidence to answer additional questions, and medical affairs trials, which examine underserved populations such as the elderly or those with comorbidities. “Our focus is to do that more in the community setting, in the places that today are not doing the other clinical trials, and increase the diversity of patients included,” he said.

In addition, Doti said, he wants to gather real-world evidence from countries beyond those typical locations that support pivotal studies. “If you see where those data are coming from, it’s from the same countries as the clinical trials,” he said.

Doti said his initiative is still “in its infancy,” but he’s optimistic that modern data collection methods can drive analyses that allow drug companies to customize treatments for different populations. “We can actually find those differences,” he said. “It will make us smarter [and able] to better understand what are the needs in different parts of the world.” 

References
1. Personified: Carlos Doti. AstraZeneca. March 13, 2023. Accessed August 6, 2023. https://bit.ly/3OksUcm
2. AstraZeneca to acquire TeneoTwo and its clinical-stage T-cell engager, strengthening haematological cancer pipeline. News release. AstraZeneca. July 5, 2022. Accessed August 7, 2023. https://www.astrazeneca.com/media-centre/press-releases/2022/astrazeneca-to-acquire-teneotwo-and-t-cell-engager.html
3. Nair R, Jacobs R, Cho SG, et al. High complete response rate with TNB-486 in relapsed/refractory follicular lymphoma: interim results from an ongoing phase 1 study. J Clin Oncol. 2023;41(suppl 16):7524. doi:10.1200/JCO.2023.41.16_suppl.7524
4. Tsuboi M, Herbst RS, John T, et al; ADAURA investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147. doi:10.1056/NEJMoa2304594
5. Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results. J Clin Oncol. 2023;41(suppl 17):LBA3000. doi:10.1200/JCO.2023.41.17_suppl.LBA3000