Neoadjuvant treatment with sotigalimab added to chemoradiotherapy is showing promise as a safe and feasible approach for patients with rectal cancer, according to data from the phase 2 INNATE trial (NCT04130854). The findings, presented at the 2024 ASTRO Annual Meeting, suggest a potential improvement in pathological complete response rates with the addition of sotigalimab.
The INNATE trial randomly assigned patients to either the sotigalimab arm or the control arm. In the sotigalimab arm, 19 patients were randomly assigned, with some receiving sotigalimab twice or refusing surgery. The control arm saw 11 patients randomly assigned, with several experiencing complications such as death during chemotherapy, disease progression, metastases at surgery, poor response to extended chemotherapy, or refusal of surgery.
Efficacy and Response Rates
Overall, 30 patients were randomly assigned and initiated therapy, with 93% completing the protocol and 80% undergoing surgery as planned. The sotigalimab arm demonstrated a pathological complete response (pCR) or resection in 22.2% of patients, compared to 14.3% in the control arm. Major responses were observed in 36.8% and 60% of patients in the sotigalimab and control arms, respectively.
"[Sotigalimab demonstrated] clear pharmacodynamic impact. There is evidence of adaptive immunity with more [information] to come," said Todd Aguilera, MD, PhD, assistant professor of radiation oncology at UT Southwestern Medical Center in Houston, Texas, during the presentation.
Trial Design and Patient Population
The INNATE trial enrolled 58 patients, randomly assigned in a 3:2 ratio over 62 months. The primary endpoint was pCR, with secondary endpoints including safety and toxicity, disease-free survival at 3 years, and overall survival at 3 years. Eligible patients were 18 years or older with newly diagnosed locally advanced rectal adenocarcinoma, stage III/high-risk stage II disease, or locally advanced disease with liver-limited metastatic cancer.
The treatment regimen involved radiation therapy at week 1, followed by leucovorin calcium, oxaliplatin, and fluorouracil (FOLFOX) from weeks 4 to 23. MRIs were conducted post-chemotherapy, followed by surgery. Sotigalimab was administered on day 3 of radiation therapy and between cycles 1 to 5 of FOLFOX.
Safety Profile
Regarding safety, grade 3/4 adverse events (AEs) occurred in 26% of patients in the sotigalimab arm versus 45% in the control arm. One toxicity-related reaction was possibly related to sotigalimab, while two were linked to radiation therapy. There were no grade 5 toxicities in the sotigalimab arm, but one occurred in the control arm due to cardiovascular arrest after perforation. Common grade 3 or higher AEs in the sotigalimab arm included intestinal obstruction (n = 2), wound infection (n = 2), abdominal pain (n = 1), and ileus (n = 1). The control arm saw events such as cholecystitis, dehydration, pulmonary embolism, and obstruction, each occurring in one patient.
