First-in-Human: Jyoti Malhotra, MD, MPH on Phase I Trials, Lung Cancer in 2026, and Yale

In this episode of The Moonlight Shift, Gina Mauro sits down with Jyoti Malhotra, MD, MPH, a thoracic medical oncologist and lung cancer specialist who has spent her career at the leading edge of early-phase drug development, to talk about what first-in-human trials actually feel like from inside the exam room, how her training in India shaped her perspective on healthcare access, and what her move to Yale Cancer Center means for the next chapter of her research.

The Conversation Nobody Fully Prepares You For

Malhotra describes the first-in-human consent conversation as one that is anything but simple. "There is the excitement about being able to offer an option to a patient for a new therapy," she says, "but at the same time there is the unknown factor — because we don't know to the full extent what the potential side effects can be, what the potential efficacy can be."

Patients in Phase I trials are monitored intensively, often spending long days in the clinic during the earliest cycles, and the conversation happens not once but many times — with the patient, the family, and across the full care team. "For many of my patients, I already know their kids, their spouses, their grandkids," she reflects. "We share pictures. We share milestones. And then we go on to the next step."

From New Delhi to Johns Hopkins to Jersey and Beyond

Malhotra trained as a physician in New Delhi before coming to the United States, where she earned a Master of Public Health in epidemiology and biostatistics from Johns Hopkins between medical school and residency — an unusual sequence she credits with giving her the analytical tools for early-career research she might otherwise have needed to outsource. Her fellowship at Mount Sinai brought her to New York, and her first faculty position at Rutgers Cancer Institute introduced her to Phase I research through an investigator-initiated trial program working directly with Rutgers scientists to move science from bench to bedside. "You are really trying to make the drug of tomorrow available to patients," she says. "And many of the patients we treat in Phase I trials are patients who have already tried standard of care therapies. They do not have a lot of great options."

The Disparities Tension That Doesn't Go Away

Her public health background runs directly into the realities of global access in drug development. For EGFR-mutant lung cancer, she notes, the United States is debating whether to add amivantamab (Rybrevant) to next-generation TKI regimens while many countries still lack access to third-generation TKIs at all. "When I work on drug development, I know that it may not reach every patient at the same time," she says. "But I know at some point it will reach the patient. And that's what I think of."

It's 2026: The Precision Medicine Conversation

When meeting a patient with newly diagnosed NSCLC for the first time, Malhotra opens with the year. "I tell them it's 2026," she says. "We don't have a one-size-fits-all approach anymore. We have a very precision-driven approach in which we try to understand what molecular subtype or mutation is driving the cancer, and we match the therapy to that." Her 2035 vision: a world where AI and precision tools allow oncologists to track and respond to cancer as it evolves in real time, and where lung cancer has become a chronic disease rather than a death sentence.

Signal or Noise?

The episode closes with the “Signal or Noise” game. Malhotra called antibody-drug conjugates in thoracic oncology and tumor mutational burden as an immunotherapy biomarker both “Noise” — while calling SCLC approaching chronic disease status and the closing of the clinical trial access gap both “Signal.” On whether lung cancer will be something we treat rather than something patients die from in fifteen years: “Hope to be ‘signal.’”

The Moonlight Shift is available on YouTube and across MJH Life Sciences' oncology platforms. New episodes, released bi-weekly, feature leading and early-career oncologists from the Tri-State corridor in peer-level conversations about where the field is going — and what it still has to work out.