Alexander I. Spira, MD, PhD, FACP, research institute director, Thoracic and Phase 1 Trial Program, Virginia Cancer Specialists Research Institute, Virginia Cancer Specialists, clinical assistant professor, Johns Hopkins, discusses the examination of RTX-240 in a phase 1 trial (NCT04372706) with solid tumors.

The open label, multidose phase 1 trial evaluated RTX-240 in patients with relapsed/refractory or locally advanced solid tumors. RTX-240 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand and IL-15TP in their native forms.

Data were presented at the 2022 AACR Annual Meeting, demonstrating that RTX-240 elicited some responses and prolonged stable disease. Phase 1 of the trial also established the recommended phase 2 dose of 5 x 1010 cells administered every 3 weeks.

Challenges with cellular therapies include their difficulty to produce and the toxicity associated with many of the current cellular therapies that require hospitalization, Spira says. This creates a need for a new generation that is less toxic off-the-shelf agents, which served as the rationale for developing RTX-240, Spira adds.

RTX-240 is unique because it is a red blood cell (RBC) therapy that engineers RBCs taken from donor cells to express 4-1BB and IL-15TP, Spira continues. The rationale is to use different aspects of the immune system to engage cancer cells and effectively attack them, Spira adds. Moreover, it is an off-the-shelf therapy and doesn't need to be personalized, Spira concludes.

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Alexander I. Spira, MD, PhD, FACP, discusses the examination of RTX-240 in a phase 1 trial with solid tumors.


Dr. Spira on the Examination of RTX-240 in a Phase 1 Trial with Solid Tumors

Alexander I. Spira, MD, PhD, FACP, medical oncologist, director, Virginia Cancer Specialists Research Institute and Phase 1 Trial Program, Virginia Cancer Specialists, discusses the role of frontline brigatinib (Alunbrig) in 

-positive non–small cell lung cancer (NSCLC).

The final results of the phase 3 ALTA-1L trial (NCT02737501) demonstrated a 52% reduction in the risk of disease progression or death with brigatinib vs crizotinib (Xalkori) in patients with 

-positive NSCLC, reflecting consistent findings with those observed in previous interim analyses.

As such, brigatinib offers a good option for the frontline treatment of this patient population, Spira says. Additionally, alectinib (Alecensa), which was granted FDA approval prior to brigatinib, is another frontline option for patients with 

Although brigatinib and alectinib have slightly different safety profiles, either agent is an appropriate option for the first-line treatment of this patient population, Spira concludes.

This activity is funded in part by Daiichi Sankyo. Content independently produced by 

Alexander I. Spira, MD, PhD, FACP, discusses the role of frontline brigatinib in ALK-positive non–small cell lung cancer.  



Dr. Spira on the Role of Frontline Brigatinib in ALK+ NSCLC 

Alexander Spira, MD, PhD, FACP, a medical oncologist and director of the Virginia Cancer Specialists Research Institute and the Phase 1 Trial Program, discusses the updated results of the phase 1 CHRYSALIS trial (NCT02609776) in 

-mutant non–small cell lung cancer (NSCLC).

During the 2021 ASCO Annual Meeting, updated findings from the CHRYSALIS trial were presented, demonstrating a 36% overall response rate with amivantamab-vmjw (Rybrevant) in combination with lazertinib (YH25448) in patients with osimertinib (Tagrisso)–relapsed, chemotherapy-naïve, 

-mutant NSCLC. The median duration of response with the combination was 9.6 months and the regimen was well tolerated.

Notably, the combination could offer patients who have progressed on a TKI an effective, chemotherapy-free, targeted option, concludes Spira.

Alexander Spira, MD, PhD, FACP, discusses the updated results of the phase 1 CHRYSALIS trial in EGFR-mutant non–small cell lung cancer.



Dr. Spira on the Updated Results of the CHRYSALIS Trial in EGFR-Mutant NSCLC 

Alexander Spira, MD, PhD, FACP, a medical oncologist and director of the Virginia Cancer Specialists Research Institute and the Phase 1 Trial Program, discusses the challenges of developing targeted therapies for patients with 

 fusion–positive non–small cell lung cancer (NSCLC). 

 fusions has generated a lot of clinical excitement in NSCLC with ongoing studies such as the phase 2 CRESTONE trial (NCT04383210) evaluating seribantumab and the phase 2 RAIN trial (NCT03805841) evaluating tarloxotinib. 

 fusions are exceedingly rare and occur in about 1% of patients with NSCLC, says Spira, who says he has not identified a patient who harbors an 

 fusion in clinical practice. Because of their rarity, identifying patients who harbor 

 fusions and enrolling them onto clinical trials is challenging, Spira explains. However, preliminary data from the CRESTONE trial appear promising for patients with solid tumors that harbor 

Alexander Spira, MD, PhD, FACP, discusses the challenges of developing targeted therapies for patients with NRG1 fusion–positive non–small cell lung cancer. 

Dr. Spira on the Challenges of Developing NRG1 Fusion–Directed Therapies in NSCLC 

Alexander Spira, MD, PhD, FACP, a medical oncologist and director of the Virginia Cancer Specialists Research Institute and the Phase 1 Trial Program, discusses the efficacy of mobocertinib (formerly TAK-788) in metastatic non–small cell lung cancer (NSCLC) that harbors 

Data from an ongoing phase 1/2 trial (NCT02716116) demonstrated an overall response rate of 26% per an independent review committee and 35% per investigator assessment with mobocertinib in previously treated patients with metastatic 

 exon 20–mutated NSCLC. Notably, the trial evaluated mobocertinib in the second-line setting for patients who previously received platinum-based chemotherapy, says Spira. 

Regarding safety, mobocertinib was associated with high rates of diarrhea and some mucositis, Spira explains. Although these adverse effects tended to be low grade, mobocertinib is an oral agent that is intended for long-term use. Therefore, even low-grade toxicities could be limiting, particularly in older patients or individuals with comorbidities, Spira concludes.

Alexander Spira, MD, PhD, FACP, discusses the efficacy of mobocertinib in metastatic non–small cell lung cancer that harbors EGFR exon 20 insertion mutations.  



Dr. Spira on the Efficacy of Mobocertinib in Metastatic EGFR Exon 20–Mutated NSCLC 

Alexander Spira, MD, PhD, FACP, a medical oncologist and director of the Virginia Cancer Specialists Research Institute and the Phase 1 Trial Program, discusses the rationale of the phase 1 CHRYSALIS trial with amivantamab (JNJ-61186372) plus lazertinib (YH25448) in 

-mutant non–small cell lung cancer (NSCLC).

The rationale for combining amivantamab with lazertinib in advanced 

-mutated NSCLC involves several factors, says Spira. With regard to the relapsed/refractory population, many patients will have 1 of 2 mutations when they relapse: a 

 mutation or amplification. That is the main area of resistance for most patients previously treated with an EGFR inhibitor such as osimertinib (Tagrisso).

Amivantamab is a bispecific antibody; therefore, it targets c-Met in an attempt to overcome c-Met resistance, as well as 

 in a different pathway. As a monoclonal antibody, it binds to the outside of the cell as opposed to a small molecule inhibitor that targets the inside of the cell. Lazertinib is very similar to osimertinib. By adding a second drug, mechanisms of resistance can potentially be overcome; there is a very strong scientific rationale for the study, concludes Spira.

Alexander Spira, MD, PhD, FACP, discusses the rationale of the phase 1 CHRYSALIS trial with amivantamab plus lazertinib in EGFR-mutant non–small cell lung cancer.

Dr. Spira on the Rationale of the CHRYSALIS Trial in EGFR-Mutant NSCLC

Alexander Spira, MD, PhD, FACP, medical oncology, hematology, Virginia Cancer Specialists, a practice within The US Oncology Network, discusses the POPLAR study for non-small cell lung cancer (NSCLC).

The phase II study randomized patients with NSCLC to atezolizumab (MPDL3280A) or docetaxel in the second- or third-line setting. Patients who were administered the anti-PD-L1 agent were treated until practitioners determined there was no longer a benefit, Spira says. Patients in the docetaxel arm were treated until disease progression.

At the interim analysis, which is not yet final, there was improved survival with atezolizumab. A correlation was also found between PD-L1 expression and efficacy of the drug. A phase III study is ongoing. Results from this study could also potentially identify a biomarker, Spira adds.

View more from the 2015 ASCO Annual Meeting

Alexander Spira, MD, PhD, FACP, medical oncology, hematology, Virginia Cancer Specialists, discusses the POPLAR study for non-small cell lung cancer (NSCLC).

Alexander Spira, MD, PhD, FACP

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