Expert discusses immunotherapy and antibody-drug conjugates against lung cancer

In a session at the World Conference on Lung Cancer in San Diego, California, September 7-10, 2024, Christian Rolfo, MD, PhD, MBA, Drhc, of the Ohio State University James Comprehensive Cancer Center, discussed immunotherapies for metastatic non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). He talked about 6 different treatment options being developed using immunotherapies and antibody-drug conjugates.

In SAFFRON-301 (NCT04921358), researchers studied tislelizumab (Tevimbra; BeiGene) plus sitravatinib for advanced or metastatic NSCLC that had progressed during or after chemotherapy and anti-PD-(L)-1. There were 187 people in the combination arm and 190 in the chemotherapy (docetaxel) arm who continued treatment until disease progression, intolerable toxicity, death, or withdrawal of consent. Median overall survival (OS) was similar in both treatment arms, and progression-free survival (PFS) was longer with the investigational therapy, but researchers reported that it did not provide the survival benefit consistent with other phase 3 trials of anti-PD-(L)-1 and tyrosine kinase inhibitors (TKIs).

“Unfortunately, the study was terminated on September 25th. [2023]due to findings associated with a serious fatal toxicity, namely pulmonary hemorrhage,” Rolfo said. Approximately 98.4% of patients on the combination experienced a treatment-emergent adverse event (TRAE), with 65.1% being grade 3 or higher.

A phase 2 trial of pembrolizumab and the Janus kinase-2 inhibitor itacitinib in metastatic NSCLC included 23 patients with a median age of 62 years and PD-L1 status of 50% to 89%, representing 60.9% of patients. The median PFS was 15.6 months, with PFS being 6.97 months in patients with PD-L1 of 50% to 89% and 23.41 months in patients with 90% to 100%, according to the presentation. The median overall survival was 53.4 months.

In Quilt 3055 (NCT03228667), investigators analyzed N-803 (Anktiva; ImmunityBio Inc) for 4 different patient cohorts: patients who had a partial (PR) or complete response (CR) and were treated with a checkpoint inhibitor after progression on standard of care; patients whose tumors had PD-L1 expression of 50% or more and who progressed on a PD-1 or PD-L1 inhibitor; patients who initially had an investigator-assessed CR or PR but were replaced after first-line checkpoint inhibitor therapy in combination with chemotherapy; and patients whose disease progressed after at least 6 months of stable disease after prior PD-1 or PD-L1 treatment. Investigators found no differences in OS across cohorts, including in second or third line or PD-L1.

Rolfo moved to antibody-drug conjugates in SCLC, where he highlighted three studies, including IDeate-Lung01 (NCT05280470), ARTEMIS-001 (NCT05276609), and TROPiCS-03 (NCT03964727).

In IDeate-Lung01, patients received either ifinatamab deruxtecan (I-DXd) at a dose of 8 mg/kg every 3 weeks (n = 40) or 12 mg/kg every 3 weeks (n = 40). The primary endpoint included overall response rate (ORR), while secondary endpoints included duration of response (DOR), PFS, OS, safety, and more. The researchers found that the higher dose was associated with a higher ORR of 54.8% compared to the lower dose of 26.1%. In addition, the intracranial ORR was 66.7% at the lower dose compared to 50% at the higher dose. The DOR was 7.9 months with the lower dose and 4.2 months with the higher dose. The data also showed that PFS and OS were longer with the higher dose, at 5.5 months and 11.8 months, respectively, compared with 4.2 months and 9.4 months, respectively, with the lower dose.

ARTEMIS-001 evaluated HS-20093, a B7-H3-targeted antibody-drug conjugate for advanced-stage SCLC. Researchers included people who had previously been treated with platinum-based chemotherapy and immunotherapy but had no more than 3 prior lines. People received either HS-20093 8 mg/kg every 3 weeks (n = 26) or 10 mg/kg every 3 weeks (n = 25). The ORR was 61.3% for those who received the 8 mg/kg dose and 50% for those who received the 10 mg/kg dose. PFS was 5.9 months and 7.3 months, respectively. In addition, researchers found that patients who had previously received platinum therapy with immunotherapy and had no history of TOP1 inhibitors achieved an ORR of 75% and 66.7%, respectively.

Finally, in the TROPiCS-03 study, participants received 10 mg/kg sacituzumab govitecan on day 1 and day 8, then in 21-day cycles until disease progression or unacceptable toxicities occurred. The primary endpoint was ORR, with secondary endpoints of DOR, OS, and safety. Of the 43 patients enrolled, 20 were platinum-resistant and 100% were treated with platinum-based chemotherapy and immune checkpoint inhibitors, the presentation said. The ORR was 41.9% with a median DOR of 4.7 months, and the DOR rate at 6 months was 48.2%. In addition, approximately 76.7% of patients experienced tumor shrinkage and 48.8% experienced a reduction in target lesion diameter of more than 30%.

In platinum-resistant patients, the ORR was 35% and in platinum-sensitive patients it was 47.8%.

“My main message from this session was that this compound, especially the combination of anti-PD1 and anti-TIM3, has not shown a survival benefit in this population with resistance to checkpoint inhibitors,” Rolfo said. “Promising effects with the new combinations of JAK-2 inhibitors and PD1 in first-line therapy, as well as with this new approach with the superagonist interleukin 15 and checkpoint inhibitors in previously treated populations.”

REFERENCES

Ferreira CGM, Rolfo C, Figueroa PU, Sands J. HOD01 – Highlights of the Day – Sunday Summaries. World Conference on Lung Cancer; San Diego, California. September 7-10, 2024.