Jonathan Goldman and Advancements in Lung Cancer Research at UCLA

Jonathan Goldman, MD, a prominent figure at UCLA Health, is at the forefront of lung cancer research and treatment. As a Hs Clinical Professor of Medicine and a lead scientist at the University of California Lung Cancer Consortium, Goldman is actively involved in studies aimed at improving early detection, treatment strategies, and overall outcomes for lung cancer patients. His work spans a range of areas, from investigating the molecular characteristics of lung cancer in never-smokers to leading clinical trials evaluating novel therapies. This article will delve into Goldman's contributions and the various initiatives he is involved in at UCLA.

Pioneering Research on Small Cell Lung Cancer (SCLC)

Goldman's research extends to understanding the nuances of Small Cell Lung Cancer (SCLC), a particularly aggressive form of the disease. Notably, he led the first and largest analysis of a rare subgroup (3-7%) of SCLC patients with no smoking history. This research highlights the rising incidence of lung cancer in never-smokers, a demographic with high unmet needs. The analysis revealed that SCLC in never-smokers occurs more frequently in females, has higher rates of EGFR and PIK3CA mutations, and exhibits lower immune infiltration markers compared to SCLC in smokers.

These findings suggest that different mechanisms may drive cancer initiation in SCLC patients who have never smoked, with potential implications for therapeutic interventions. Historically, SCLC clinical trials have often enrolled all patients without considering molecular features. However, recent research, including Goldman's work, emphasizes the importance of focusing on distinct molecular subgroups to tailor treatments more effectively. This study was presented at the ESMO Congress in September 2022.

Clinical Trial: Tarlatamab for Limited-Stage SCLC

Jonathan Goldman is the Principal Investigator of a Phase 3 clinical trial at UCLA, which started in February 2024 and is expected to end around October 2029. The study, titled "A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Tarlatamab Therapy in Subjects With Limited-Stage Small-Cell Lung Cancer (LS-SCLC) Who Have Not Progressed Following Concurrent Chemoradiation Therapy," aims to evaluate the efficacy of tarlatamab compared to placebo in patients with limited-stage SCLC who have not progressed after concurrent chemoradiation therapy.

Tarlatamab, also known as AMG 757, is being investigated for its potential to improve progression-free survival (PFS) in these patients. The trial has specific eligibility criteria, including:

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Age 18 years and up
Histologically or cytologically confirmed SCLC
Diagnosed and treated for LS-SCLC with concurrent chemotherapy and radiotherapy
Completion of chemoradiotherapy without progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
Minimum life expectancy of 12 weeks
Adequate organ function
Resolution of toxicities attributed to concurrent chemoradiotherapy to grade ≤ 1, with some exceptions

Exclusion criteria include extensive-stage SCLC, prior diagnoses of transformed non-small-cell lung cancer (NSCLC), evidence of interstitial lung disease, history of other malignancies within the past 2 years (with certain exceptions), and certain other medical conditions and prior therapies.

The trial is being conducted at multiple locations, including the University of California Los Angeles and Valkyrie Clinical Trials in Los Angeles.

Healthy Lungs California Initiative

Goldman is also deeply involved in the Healthy Lungs California initiative, a collaborative effort aimed at increasing early lung cancer detection and reducing deaths from the disease. This initiative, supported by a five-year partnership between the University of California Lung Cancer Consortium and AstraZeneca, brings together researchers from five UC campuses: UC Davis, UC Irvine, UCLA, UC San Diego, and UCSF.

Addressing Screening Gaps

Lung cancer is the leading cause of cancer-related deaths in the United States. Despite the U.S. Preventive Services Task Force's updated guidelines in 2021 that increased the number of people eligible for screening, actual screening rates remain extremely low. The Healthy Lungs California initiative was launched in response to findings by the American Lung Association that showed alarmingly low screening rates among high-risk individuals, particularly in California, which had the lowest screening rate in the country (less than 1 percent).

The updated guidelines define high-risk individuals as those who:

Are 50-80 years old
Have smoked 20 "pack years" (smoked a pack of cigarettes a day per year)
Still smoke or quit within the past 15 years

Collaborative Approach

The UC Lung Cancer Consortium, coordinated by Amy L. Cummings, M.D., Ph.D., a thoracic oncologist and research scientist at the UCLA Health Jonsson Comprehensive Cancer Center, is central to this collaboration. Jonathan Goldman chairs the consortium, providing leadership and direction to the initiative.

"This important initiative allows us to address critical gaps in screening and assess environmental factors-such as the impact of pollution and wildfires-that may increase lung cancer risk," said Goldman. "Together with AstraZeneca and community members, we will be working to expand our efforts further to help improve early lung cancer detection screening rates."

Key Focus Areas

The Healthy Lungs California initiative is concentrating its efforts on several key areas:

Expanding Community Education and Outreach: Providing grants, branding support, and expertise for events designed to improve early lung cancer detection and screening among high-risk individuals.
Supporting New Screening Programs: Offering grants, best practice sharing, and toolkits to help organizations start early lung cancer detection and screening programs in their communities.
Addressing Health Disparities: Identifying interventions to improve early detection rates in communities with disproportionately high rates of lung cancer.
Exploring Innovative Approaches: Piloting programs that trial AI-assisted incidental pulmonary nodule (IPN) review to alleviate bottlenecks in communities with medical expertise shortages.
Informing Public Policy: Sharing insights and scalable solutions to help shape early lung cancer detection and screening policies in California and nationwide.
Evaluating Environmental Factors: Assessing early lung cancer detection in individuals with a history of environmental exposure to wildfires, air pollution, and/or first-degree relatives diagnosed with lung cancer.
Engaging Community Partners: Involving community partners in the initiative through a partnership steering committee, comprising representatives from the UC Lung Cancer Consortium, AstraZeneca, and a Community Advisory Board.

Other Research and Clinical Activities

In addition to his work on SCLC and the Healthy Lungs California initiative, Jonathan Goldman has been involved in numerous other research projects and clinical activities related to lung cancer and other cancers. These include:

Clinical Trials

Phase II Trial of Ivonescimab for Thymic Carcinoma: Goldman is involved in a phase II trial evaluating the effectiveness of ivonescimab in treating patients with thymic carcinoma. This trial has specific inclusion and exclusion criteria related to pregnancy, contraception, prior treatments, and medical conditions.
LIBRETTO-432: A phase III study of adjuvant selpercatinib or placebo in stage IB-IIIA RET fusion-positive non-small-cell lung cancer.

Publications

Goldman has co-authored numerous publications in prestigious medical journals, covering a wide range of topics related to lung cancer and other cancers. Some notable publications include:

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"Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC" (N Engl J Med, Tsuboi et al.)
"Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions" (N Engl J Med, Zhou et al.)
"Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer" (Nat Med. Herbst et al.)
"CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors" (Nature, Skoulidis et al.)
"Neratinib Efficacy in Patients With EGFR Exon 18-Mutant Non-Small-Cell Lung Cancer: Findings From the SUMMIT Basket Trial" (Clin Lung Cancer, Goldman et al.)

These publications demonstrate Goldman's commitment to advancing the understanding and treatment of lung cancer through rigorous scientific inquiry.

Patient Care

Beyond research, Jonathan Goldman is also dedicated to providing excellent patient care. He treated Nikki Moreno, a 42-year-old mother of two, who was diagnosed with stage IV lung cancer. Moreno's case highlights the fact that lung cancer can affect anyone, including women who have never smoked. Goldman noted that the ALK mutation found in Moreno's cancer is often highly responsive to targeted therapy, offering a significant treatment option.

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