Dr Porter on the Potential Role for Taletrectinib in ROS1+ NSCLC

Jason Porter, MD, medical oncologist, hematologist, director, Lung Cancer Disease Research Group, West Cancer Center and Research Institute, discusses the potential role of the next-generation TKI taletrectinib (AB-106) in patients with 

-positive non–small cell lung cancer (NSCLC), according to data from the phase 2 TRUST-II trial (NCT04919811).

Interim results from the international, multicenter, open-label, single-arm TRUST-II trial were presented at the 

, and showed that taletrectinib demonstrated robust and durable tumor responses. Confirmed overall response rates with the agent were 92.0% (95% CI, 74.0%-99.0%) and 57.1% (95% CI, 34.0%-78.2%) in evaluable patients who were TKI naive and TKI pretreated, respectively.

Furthermore, the intracranial overall response rates in patients with measurable brain metastases were 80% (95% CI, 28.4%-99.5%) in the TKI-naive population and 62.5% (95% CI, 24.5%-91.5%) in the TKI-pretreated population.

These data have clinical implications for reshaping treatment approaches in 

-positive disease, Porter begins, adding that the agent’s impact may be comparable to that of crizotinib (Xalkori) in 

-positive NSCLC. Taletrectinib exhibits notable activity against 

 mutations, which are associated with resistance to crizotinib and earlier ROS1 inhibitors, Porter explains. This extends the potential applicability of taletrectinib to patients who have previously progressed on crizotinib, he says.

Notably, another key feature of taletrectinib is its efficacy against central nervous system (CNS) involvement, which has the potential to address unmet needs associated with crizotinib, Porter adds. Although crizotinib demonstrates CNS activity, recent ALK inhibitors have showcased improved efficacy in the CNS, he details. Taletrectinib shows similarly improved activity in patients with 

-mutant disease, potentially becoming a preferred choice for its enhanced CNS penetration, Porter states.

 resistance mutation combined with increased CNS efficacy positions taletrectinib as a promising candidate for patients with 

 mutations who are at a higher risk of CNS disease, Porter emphasizes. These observed benefits could position taletrectinib as a prospective first-line agent for patients with 

In addition to taletrectinib's promising efficacy, it is important to consider potential toxicities associated with this agent, particularly neurotoxicity or CNS toxicity, Porter continues. However, taletrectinib was developed, in part, to overcome some of the CNS toxicity observed with crizotinib and entrectinib (Rozlytrek), he notes. Despite originating in a small patient population, the encouraging data from TRUST-II underscore the value of taletrectinib as a potential option for patients with 

-positive NSCLC in need of an effective and safe treatment, Porter concludes.

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Jason Porter, MD, discusses the potential role of the next-generation TKI taletrectinib in patients with ROS1-positive non–small cell lung cancer, according to data from the phase 2 TRUST-II trial.

Jason Porter, MD, medical oncologist, hematologist, director, Lung Cancer Disease Research Group, West Cancer Center and Research Institute, discusses the 3-year follow-up data from the phase 3 CheckMate-9LA trial (NCT03215706) done in patients with metastatic non–small cell lung cancer (NSCLC).

CheckMate-9LA evaluated nivolumab (Opdivo) and ipilimumab (Yervoy) plus chemotherapy vs chemotherapy alone as a first-line treatment for patients with metastatic NSCLC.

The 3-year follow-up data showed encouraging survival benefits with the addition of nivolumab and ipilimumab to chemotherapy, irrespective of patients’ histology or PD-L1 status, Porter says. The 3-year overall survival (OS) rates for patients who received the combination therapy vs chemotherapy alone were 27% and 19%, respectively, Porter adds. Moreover, patients with PD-L1–negative disease who were treated with combination therapy achieved a 3-year OS rate of 25% vs 15% in those who received chemotherapy alone, Porter explains.

Additionally, patients with a PD-L1 expression of at least 1% who received nivolumab/ipilimumab plus chemotherapy experienced a 3-year OS rate of 28% compared with 19% in those who received chemotherapy alone, Porter emphasizes.

Patients who have symptomatic disease or greater disease burden will typically need chemotherapy, Porter adds. Improving outcomes in these patients with only 2 cycles of chemotherapy in CheckMate-9LA is an exciting development, Porter concludes.

Jason Porter, MD, discusses the 3-year follow-up data from the phase 3 CheckMate-9LA trial done in patients with metastatic non–small cell lung cancer.

Dr. Porter on the 3-Year Follow-Up Data From the CheckMate-9LA Trial in NSCLC

Kevin Kalinsky, MD, MS, is a professor and director of the Division of Medical Oncology in the Department of Hematology and Medical Oncology at Emory University School of Medicine; and the Louisa and Rand Glenn Family Chair in Breast Cancer Research and director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University in Atlanta, Georgia.

Jason Porter, MD, Janakiraman Subramanian, MD, Natalie S. Calendar, MD, Parameswaran Hari, MD, MRCP, and Kevin Kalinsky, MD, MS, discuss the importance of the Institutional Perspectives in Cancer (IPC) webinars.

The IPC webinars allow oncologists to review and present large sets of data to their peers who may not be able to attend meetings or who have a specific focus in a particular tumor type, Porter, a oncologist/hematologist, and director, Lung Cancer disease research group, West Cancer Center and Research Institute, says. These programs allow attendees to consume and digest data easily and take what they learned back to their clinical practice, Porter notes. 

According to Subramanian, a medical oncologist and director of Thoracic Oncology, Center for Precision Medicine, at Saint Luke’s Cancer Institute, many colleagues have shared about how useful they found these webinars to be. Additionally, attendees who were not oncologists, such as surgeons or pulmonologists, expressed excitement in how the field of oncology has advanced in recent years, Janakiraman explains.

As so many advances have been made across multiple tumor types, these webinars serve as a way to help consolidate and distill information in a useful way, Callander, a professor of medicine in the Division of Hematology/Oncology at the University of Wisconsin Carbone Cancer Center, adds.

The COVID-19 pandemic has shown that it is possible to utilize technology to deliver short, precise information to a wide audience, Hari, the Armand J. Quick/William F. Stapp Professor of Hematology, and the chief of the Division of Hematology/Oncology, Department of Medicine, at the Medical College of Wisconsin, notes. For those oncologists who typically focus on just 1 tumor type, it is important that those experiences get shared with as many healthcare providers as possible to extend benefits to patients, Hari explains. 

Despite the pandemic, it is important for healthcare providers to be able to come together to discuss data and recent findings, Kalinsky, director of the Glenn Family Breast Center and Breast Medical Oncology at Winship Cancer Institute, and acting associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, concludes.

Jason Porter, MD, Subramanian Janakiraman, MD, Natalie S. Calendar, MD, Parameswaran Hari, MD, MRCP, and Kevin Kalinsky, MD, MS, discuss the importance of the Institutional Perspectives in Cancer webinars. 


Examining the Importance of the Institutional Perspectives in Cancer Webinars

Jason Porter, MD, oncologist/hematologist, director, Lung Cancer disease research group, West Cancer Center and Research Institute, discusses potential sequencing strategies with antibody-drug conjugates (ADCs) and TKIs in HER2-positive lung cancer.

Although cross-trial comparisons are not recommended, the potential integration of TKIs, such as mobocertinib and poziotinib, and ADCs, such as fam-trastuzumab deruxtecan-nxki (Enhertu), for patients with HER2-positive lung cancer raises the question of sequencing, Porter explains. 

The TKIs are oral medications that target HER2 specifically and do not require intravenous infusion, Porter says. Given the ongoing COVID-19 pandemic, the utility of outpatient therapy with the TKIs may be preferrable to trastuzumab deruxtecan, Porter explains. However, response and disease control rates with trastuzumab deruxtecan were impressive, and the ADC does not appear to confer the same toxicities that have been observed with the TKIs, Porter says. 

Therefore, sequencing is not clear with ADCs and TKIs in HER2-positive lung cancer. There are benefits and drawbacks to utilizing either therapy first, Porter says. Potentially, combination strategies with ADCs and TKIs or either therapy plus chemotherapy will optimize the benefits with these agents in patients with HER2-positive lung cancer, concludes Porter. 

Jason Porter, MD, discusses potential sequencing strategies with antibody-drug conjugates and TKIs in HER2-positive lung cancer.  



Jason Porter, MD

Articles

Dr Porter on the Potential Role for Taletrectinib in ROS1+ NSCLC

Dr. Porter on the 3-Year Follow-Up Data From the CheckMate-9LA Trial in NSCLC

Examining the Importance of the Institutional Perspectives in Cancer Webinars

Dr. Porter on Potential Sequencing With ADCs and TKIs in HER2+ Lung Cancer