Thomas Marron, MD, PhD, discusses how findings from the DeLLphi-303 trial are shaping the use of tarlatamab across treatment settings in small cell lung cancer.

“Tarlatamab is currently our preferred second-line therapy [in extensive-stage small cell lung cancer]. Most patients receive induction chemoimmunotherapy followed by immunotherapy maintenance, but the majority ultimately experience recurrence. We [have observed] not only amazing response rates but [also notable] durability of response [with tarlatamab]."

Thomas Marron, MD, PhD, director of the Early Phase Trials Unit at the Tisch Cancer Institute and a tenured professor of medicine at Mount Sinai, discussed how emerging data from the phase 1b DeLLphi-303 trial (NCT05361395) have informed the evolving role of tarlatamab (Imdelltra) in the treatment paradigm for extensive-stage small cell lung cancer (SCLC).

DeLLphi-303 evaluated tarlatamab, a DLL3-directed bispecific T-cell engager, in combination with frontline chemoimmunotherapy or in the maintenance setting following induction therapy. Initial data readouts during the 

International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer

 demonstrated that adding tarlatamab to maintenance durvalumab (Imfinzi) or atezolizumab (Tecentriq) improved survival vs maintenance anti–PD-L1 therapy alone, with a median OS of 25.3 months (n = 88; 95% CI, 20.3-not evaluable). The disease control rate (DCR) was 60%, which exceeded historical expectations for extensive-stage SCLC, according to Marron.

Updated results from the frontline chemoimmunotherapy cohort shared at the 

 demonstrated an ORR of 71% (95% CI, 61%-80%), with a complete response rate of 5% and a partial response rate of 66%, with the regimen at a median follow-up of 13.8 months (95% CI, 12.5-15.0).

Based on these findings, tarlatamab has become the preferred second-line therapy for patients who progress after induction chemoimmunotherapy and maintenance immunotherapy. Marron emphasized that tarlatamab not only induces meaningful response rates but also demonstrates durable benefit, contributing to a survival “tail” that suggests a subset of patients may achieve long-term disease control.

However, he noted that the current data have not yet been compared with standard-of-care therapy in randomized trials and that the relative contribution of individual components within combination regimens have yet to be fully understood.

Ongoing and future studies informed by DeLLphi-303 will therefore be critical to confirm the optimal role for tarlatamab in both the front and second lines in SCLC, Marron explained. Mature findings will help clarify sequencing strategies, define the populations most likely to benefit, and guide where the SCLC treatment paradigm should advance next, he concluded.

Videos

Dr Marron on the Evolving Role of Tarlatamab in SCLC

Thomas Marron, MD, PhD, discusses cancer's attack on the immune system. 

Cancer Hijacks Your Bone Marrow and Your Immune System

Thomas Marron, MD, PhD, of The Tisch Cancer Institute at Mount Sinai, discusses the ways cancer attacks the bone marrow and immune system. 

 Cancer Hijacks Your Bone Marrow and Your Immune System: What Are You Going to Do About It?

Thomas Urban Marron, MD, PhD, an assistant director of early phase and immunotherapy clinical trials at the Tisch Cancer Institute, and an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, describes the patient population included in a phase 1 study (NCT02721043) examining the use of PGV-001, a neoantigen cancer vaccine, across different malignancies.

The trial enrolled patients who had at least a 30% chance of disease recurrence, which was based on factors such as tumor stage, and other histologic characteristics, according to Marron. For patients with multiple myeloma, it is almost guaranteed that they will experience recurrence following autologous stem cell transplant, he notes. 

Similarly high rates of recurrence have been observed in patients with recurrent head and neck cancer who are undergoing a second surgery, a population that comprised a notable portion of study participants (n = 6). Additionally, patients with advanced lung cancer experience similar higher rates of recurrence, Marron adds. Nearly all patients received an adjuvant therapy following treatment with surgery or transplant followed by PGV-001, Marron concludes.

Thomas Urban Marron, MD, PhD, describes the patient population included in a phase 1 study examining the use of PGV-001, a neoantigen cancer vaccine, across different malignancies.

Dr. Marron on the Population Included in a Phase 1 Study of PGV-001 Neoantigen Cancer Vaccine

Thomas Urban Marron, MD, PhD, an assistant director of early phase and immunotherapy clinical trials at the Tisch Cancer Institute, and an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, discusses primary objectives of a study examining the use of an adjuvant personalized neoantigen peptide vaccine in several malignancies.

The first goal was to determine the safety of the vaccine, which appeared to be well tolerated across the patient population, according to Marron. Patients experienced minimal injection adverse effects, which can be attributed to polyinosinic-polycytidylic, a viral mimic that helps to stimulate the immune system, Marron explains. Additionally, investigators set out to determine the feasibility of manufacturing and administering the vaccine, Marron says.

Fifteen patients with a range of malignancies, including non–small cell lung cancer, ductal or lobular breast cancer, head and neck cancer, ovarian or fallopian tube epithlieal carcinoma, prostate cancer, urothelial cancer, renal cell carcinoma, and multiple myeloma were enrolled to the trial, 13 of whom were vaccinated. Of the 2 patients who were not vaccinated, 1 with lung cancer experienced progressive disease while receiving adjuvant doublet chemotherapy, while the other patient, who was still in remission, selected a study that was closer to their residence. In total, 11 patients received all 10 vaccines, with the remaining 2 patients received 7 and 9 vaccines, respectively. Although the approach is feasible, this strategy requires several visits to the clinic, Marron notes.

The final objective of the study was to determine the immunogenicity of the vaccine, Marron notes. Although the study population is small, investigators observed robust induction of CD4 and CD8 T-cell response, Marron concludes.

Thomas Urban Marron, MD, PhD, discusses primary objectives of a study examining the use of an adjuvant personalized neoantigen peptide vaccine in several malignancies.


Dr. Marron on an Adjuvant Personalized Neoantigen Peptide Vaccine for Several Malignancies 

Thomas Marron, MD, PhD, assistant professor of medicine, hematology, and medical oncology at Mount Sinai Hospital, discusses the potential benefit of shortening the length of immunotherapy treatment in melanoma.  

The goal of cure may be within sight since the introduction of immunotherapy, says Marron. However, a remaining question in melanoma is when to stop treatment with immunotherapy. In previous clinical trials, nivolumab (Opdivo) was given indefinitely while pembrolizumab (Keytruda) was given for 2 years. 

It is hypothesized that prolonged treatment may not be necessary for these patients, explains Marron. Additionally, extended therapy may increase the chance of developing immune-related adverse events.

Shortening treatment duration would lessen the physical and financial burdens immunotherapy can cause for patients, concludes Marron.

Thomas Marron, MD, PhD, discusses the potential benefit of shortening the length of immunotherapy treatment in melanoma.

Thomas Marron, MD, PhD

Articles

Dr Marron on the Evolving Role of Tarlatamab in SCLC

Cancer Hijacks Your Bone Marrow and Your Immune System: What Are You Going to Do About It?

Dr. Marron on the Population Included in a Phase 1 Study of PGV-001 Neoantigen Cancer Vaccine

Dr. Marron on an Adjuvant Personalized Neoantigen Peptide Vaccine for Several Malignancies

Dr. Marron on Shortening Treatment Duration of Immunotherapy in Melanoma