Oncology Daily Report: 01/25/2024

Phase 3 Studies

Gastric Cancer (Early)

A phase 3 multicenter randomized controlled clinical trial (SENORITA trial) investigated the effect of laparoscopic sentinel node navigation surgery (LSNNS) in 527 patients with early gastric cancer and found that the 5-year disease-free survival, overall survival, and disease-specific survival did not differ significantly between LSNNS and laparoscopic standard gastrectomy groups, suggesting LSNNS could be an alternative treatment option for EGC (1).

Reference

Hur H, Lee YJ, Kim YW, Min JS, Yoon HM, Yeong An J, Eom BW, Seok Cho G, Park YK, Jung MR, Park JH, Hyung WJ, Jeong SH, Kook MC, Han M, Nam BH, Ryu KW. Clinical Efficacy of Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: 5-year Results of the SENORITA Trial. Ann Surg. 2024 Jan 25. doi: 10.1097/SLA.0000000000006219. Epub ahead of print. PMID: 38269605.

Non-Small Cell Lung Cancer

A phase III open-label, randomized, multicenter study investigated the effect of Iruplinalkib (180 mg once daily with a 7-day run-in at 60 mg once daily) versus Crizotinib (250 mg twice daily) in 292 patients with ALK TKI-naïve locally advanced or metastatic ALK-positive NSCLC and found that the median progression-free survival (PFS) was significantly longer in the Iruplinalkib group (27.7 months) compared to the Crizotinib group (14.6 months) with a hazard ratio (HR) of 0.34 (p<0.0001) (1). The objective response rate (ORR) was 93.0% in the Iruplinalkib group and 89.3% in the Crizotinib group. The intracranial ORR was 90.9% in the Iruplinalkib group for patients with measurable baseline CNS metastases, compared to 60.0% in the Crizotinib group. The incidence of grade 3 or 4 treatment-related adverse events was 51.7% in the Iruplinalkib group and 49.7% in the Crizotinib group.

Reference

Shi Y, Chen J, Yang R, Wu H, Wang Z, Yang W, Cui J, Zhang Y, Liu C, Cheng Y, Liu Y, Shan J, Wang D, Yang L, Hu C, Zhao J, Cao R, Tan B, Xu K, Si M, Li H, Mao R, Li L, Kang X, Wang L. Iruplinalkib (WX-0593) versus crizotinib in ALK TKI-naïve locally advanced or metastatic ALK-positive non-small cell lung cancer: interim analysis of a randomized, open-label, phase III study (INSPIRE). J Thorac Oncol. 2024 Jan 25:S1556-0864(24)00033-9. doi: 10.1016/j.jtho.2024.01.013. Epub ahead of print. PMID: 38280448.

Phase 2 Studies

B-cell Lymphoma

A phase II Japanese trial investigated the feasibility and tolerability of a 90-minute infusion of rituximab (375 mg/m2 at a concentration of 4 mg/mL) in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone in 32 Japanese patients with previously untreated follicular lymphoma or diffuse large B-cell lymphoma (1). The study found that the 90-minute infusion of rituximab was feasible and tolerable, with no grade 3 or higher infusion-related reactions reported in cycle 2 of treatment. The most common infusion-related reaction symptoms were pruritus, hypertension, and oropharyngeal discomfort, and no new safety signals were observed.

Reference

Saito T, Nagai H, Izutsu K, Ando K, Igarashi T, Izumi T, Ohashi Y, Kamiyama S, Ishizawa K, Tobinai K. A phase II Japanese trial of 90-minute rituximab infusion for untreated B-cell lymphoma. Jpn J Clin Oncol. 2024 Jan 25:hyad193. doi: 10.1093/jjco/hyad193. Epub ahead of print. PMID: 38271157.

Squamous Cell Carcinoma (Anal)

A phase II multicenter clinical trial investigated the effect of pembrolizumab in 32 patients with metastatic or locally advanced incurable anal squamous cell carcinoma and found an objective response rate of 9.4% and a median progression-free survival of 2.2 months (1). Despite high HPV positivity, most patients had low levels of tumor-associated CD8+PD-1+ T cells, indicating resistance to pembrolizumab. Long-term responses were rare, observed in one trial participant (5.3 years) and three patients from a retrospective cohort (2.5, 6, and 8 years), all with HPV-positive tumors, no liver metastases, and achieving radiological complete responses.

Reference

Huffman BM, Singh H, Ali LR, Horick N, Wang SJ, Hoffman MT, Metayer KA, Murray S, Bird A, Abrams TA, Biller LH, Chan JA, Meyerhardt JA, McCleary NJ, Goessling W, Patel AK, Wisch JS, Yurgelun MB, Mouw K, Reardon B, Van Allen EM, Zerillo JA, Clark JW, Parikh A, Mayer RJ, Schlechter B, Ng K, Kumar S, Del Vecchio Fitz C, Kuperwasser C, Hanna GJ, Coveler AL, Rubinson DA, Welsh EL, Pfaff K, Rodig S, Dougan SK, Cleary JM. Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders. J Immunother Cancer. 2024 Jan 25;12(1):e008436. doi: 10.1136/jitc-2023-008436. PMID: 38272561; PMCID: PMC10824013.

Phase 1 Studies

Hepatocellular Carcinoma

A phase 1 trial investigated the combination of navitoclax and sorafenib in 25 patients with relapsed or refractory solid tumors, including a hepatocellular carcinoma expansion cohort (1). The maximum tolerated dose was navitoclax 150 mg daily plus sorafenib 400 mg twice daily. Among all patients, the most common grade 3 toxicity was thrombocytopenia, with no grade 4 or 5 toxicities reported. Six patients in the hepatocellular carcinoma cohort achieved stable disease, but no partial or complete responses were observed. The combination showed limited efficacy, suggesting this treatment approach may not be viable for advanced hepatocellular carcinoma.

Reference

Emiloju OE, Yin J, Koubek E, Reid JM, Borad MJ, Lou Y, Seetharam M, Edelman MJ, Sausville EA, Jiang Y, Kaseb AO, Posey JA, Davis SL, Gores GJ, Roberts LR, Takebe N, Schwartz GK, Hendrickson AEW, Kaufmann SH, Adjei AA, Hubbard JM, Costello BA. Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort. Invest New Drugs. 2024 Jan 25. doi: 10.1007/s10637-024-01420-8. Epub ahead of print. PMID: 38270822.