Phase 2 IMscin002 Study Shows Patients With NSCLC Prefer Subcutaneous Atezolizumab

Federico Cappuzzo, MD

Patients with non–small cell cancer (NSCLC) preferred treatment with subcutaneous (SC) atezolizumab (Tecentriq) compared with the intravenous (IV) formulation, according to data from the phase 2 IMscin002 trial (NCT03735121) presented at the 2024 European Lung Cancer Congress.¹

Findings from the crossover period showed that 70.7% of 123 patients preferred SC atezolizumab vs 21.1% who preferred the IV formulation. Moreover, 8.1% of patients (n = 10/123) had no preference between the SC and IV forms. The primary reasons for preferring the SC option included: less time in the clinic (64.4%), administration was more comfortable (46.0%), and treatment was less emotionally distressing (29.9%).

Additionally, during the continuation period, 79.4% of 107 patients picked treatment with SC atezolizumab compared with 20.6% of those who selected the IV formulation.

“SC usage of atezolizumab gave relevant advantage for the patients and the institutions, and these results support all the previous findings that SC atezolizumab is equivalent to IV use,” lead study author Federico Cappuzzo, MD, director of Medical Oncology at Azienda Unità Sanitaria Locale della Romagna-Ravenna in Italy, said in a presentation of the data.

In January 2024, the European Commission granted marketing authorization for subcutaneous atezolizumab co-formulated with Enhanze, a recombinant human hyaluronidase enzyme rHuPH20, for all approved indications of IV atezolizumab.² That regulatory decision was supported by data from the phase 1b/3 IMscin001 trial (NCT03735121).

IMscin002 was an open-label, crossover study that enrolled patients at least 18 years of age with EGFR/ALK wild-type NSCLC who had an ECOG performance status of 0 or 1. Patients were allowed to have resected stage II to IIIB disease that was PD-L1 positive (≥1%) and previously treated with adjuvant chemotherapy; or stage IV NSCLC that was PD-L1 high (≥50%) and naive to chemotherapy.1

All patients were randomly assigned 1:1 to receive 3 cycles of SC atezolizumab at 1875 mg once every 3 weeks for 3 cycles, followed by IV atezolizumab at 1200 mg once every 3 weeks for 3 cycles; or the inverse sequence for 3 cycles each. During the continuation period following 6 cycles of treatment, patients were permitted to choose between the SC and IV formulations.

Patients were stratified by disease stage (II vs III vs IV) and type of surgery (no surgery vs pneumonectomy vs any other surgery).

The study’s primary end point was the proportion of patients who preferred SC atezolizumab vs the IV formulation at day 1 of cycle 6 during the crossover period, as assessed by a patient preference questionnaire. Secondary end points included patient-reported satisfaction, patients’ choice of treatment during the continuation period, and safety.

Among all patients (n = 179), the median age was 67 years (range, 39-91). The majority of patients were male (67%), White (83%), had an ECOG performance status of 1 (55%), were former smokers (64%), had not received prior systemic therapy (60%), had stage IV disease at the time of enrollment (65%), had nonsquamous histology (63%), and had not undergone surgery (58%).

Additional data showed that 85.8% of patients were very satisfied or satisfied with SC atezolizumab compared with 75.2% of patients for the IV formulation. Specifically for SC atezolizumab, patients (n = 127) were very satisfied (40.9%), satisfied (44.9%), neither satisfied nor dissatisfied (11.0%), dissatisfied (2.4%), or very dissatisfied (0.8%). For IV atezolizumab, patients (n = 123) were very satisfied (26.3%), satisfied (48.9%), neither satisfied nor dissatisfied (21.1%), dissatisfied (1.5%), or very dissatisfied (2.3%).

Cappuzzo also noted that SC atezolizumab does not need to be prepared in sterile conditions and can be prepared in the ward, and he explained that nurses in the ward could prepare the agent three times faster than pharmacists in the pharmacy.

Safety data were consistent with the known profile of atezolizumab, with no new safety concerns identified. Furthermore, switching between the SC and IV formulations of atezolizumab was well tolerated, irrespective of sequence. Notably, rates of infusion-site reactions or infusion-site reaction adverse effects (AEs) did not increase when switching between the SC and IV formulations, irrespective of the first treatment used.

During crossover, in patients who started with SC atezolizumab in cycles 1 to 3 (n = 86) and received IV atezolizumab in cycles 4 to 6 (n = 71), the rates of any-grade AEs were 54.7% with the SC formulation and 53.5% with the IV formulation. The rates of treatment-related AEs (TRAEs) were 36.0% and 31.0%, respectively. One patient (1.2%) experienced a TRAE with SC atezolizumab that proved fatal.

The rates of serious AEs were 12.8% and 5.6% for SC atezolizumab in cycles 1 to 3 and IV atezolizumab in cycles 4 to 6, respectively. Serious TRAEs occurred at rates of 4.7% and 2.8%, respectively. For SC atezolizumab, the rates of grade 3/4 AEs and grade 3/4 TRAEs were 15.1% and 5.8%, respectively; those respective rates were 9.9% and 1.4% for IV atezolizumab. The rates of AEs leading to treatment discontinuation and interruption for SC atezolizumab were 5.8% and 10.5%, respectively, vs 2.8% and 9.9% for IV atezolizumab

In patients who received IV atezolizumab in cycles 1 to 3 (n = 89) and SC atezolizumab in cycles 4 to 6 (n = 69), the rates of any-grade AEs were 62.9% and 39.1%, respectively. The rates of TRAEs were 31.5% and 30.4%, respectively, and 1 patient each experienced a fatal TRAE with the IV formulation (1.1%) and with the SC formulation (1.4%).

The rates of serious AEs were 12.4% and 2.9% for IV atezolizumab in cycles 1 to 3 and SC atezolizumab in cycles 4 to 6, respectively. Serious TRAEs occurred at rates of 4.5% and 2.9%, respectively. For IV atezolizumab, the rates of grade 3/4 AEs and grade 3/4 TRAEs were 16.9% and 6.7%, respectively; those rates were both 0% for SC atezolizumab. The rates of AEs leading to treatment discontinuation and interruption for IV atezolizumab were both 7.9% vs 2.9% for both with SC atezolizumab.

Editor’s Note: Dr Cappuzzo disclosed serving as an invited speaker, advisory board member, and in an advisory role for F. Hoffman-La Roche Ltd., AstraZeneca, Bristol Myers Squibb, Pfizer, Takeda Pharmaceuticals, Eli Lilly and Company, Bayer AG, Amgen Inc, Sanofi SA, PharmaMar, Novocure, Mirati Therapeutics, Inc., Galecto Biotech, OSE Immunotherapeutics, Illumina, Inc., Thermofisher, and MSD.

References

1. Cappuzzo F, Zvirbule Z, Korbenfeld E, et al. Primary results from IMscin002: a study to evaluate patient- and healthcare professional-reported preferences for atezolizumab subcutaneous vs intravenous for the treatment of non-small cell lung cancer. Presented at: 2024 European Lung Cancer Congress; March 20-23, 2024; Prague, Czech Republic. Abstract 244MO.
2. Halozyme announces Roche receives European Commission approval of Tecentriq SC with Enhanze representing the EU’s first subcutaneous PD-(L)1 cancer immunotherapy for multiple cancer types. News release. Halozyme Therapeutics. January 16, 2024. Accessed March 22, 2024. https://www.prnewswire.com/news-releases/halozyme-announces-roche-receives-european-commission-approval-of-tecentriq-sc-with-enhanze-representing-the-eus-first-subcutaneous-pd-l1-cancer-immunotherapy-for-multiple-cancer-types-302035190.html