Colorectal cancer – recent phase I/II trials of interest

Here are Colorectal cancer trials with the best results and highest response rates from selected abstracts:

1. Divarasib plus Cetuximab:
   • Response Rate: 62.5%
   • Details: This combination was evaluated in KRAS G12C-positive colorectal cancer. The objective response rate (ORR) was 62.5% (95% confidence interval: 40.6%, 81.2%) in KRAS G12C inhibitor-naive patients.
   • Study Identifier: NCT04449874
2. Nintedanib and Capecitabine:
   • Response Rate: 42% 18-week progression-free survival (PFS)
   • Details: Evaluated in refractory metastatic colorectal cancer. The combination showed a median overall survival of 8.9 months with 42% of patients having an 18-week PFS.
3. Anlotinib plus Irinotecan:
   • Response Rate: 25.8%
   • Details: This combination was used for the second-line treatment of metastatic colorectal cancer. Eight patients achieved partial response (PR) and the disease control rate (DCR) was 93.5%.
4. Cabozantinib plus Durvalumab:
   • Response Rate: 30%
   • Details: Evaluated in advanced chemo-refractory proficient mismatch repair or microsatellite stable (pMMR/MSS) gastrointestinal malignancies, including colorectal cancer. The overall response rate was 30%.
   • Study Identifier: Not specified
5. Sotorasib with Panitumumab:
   • Response Rate: 30%
   • Details: Evaluated in chemotherapy-refractory KRAS(G12C)-mutated metastatic colorectal cancer. The confirmed ORR was 30% (95% confidence interval 16.6%, 46.5%).
   • Study Identifier: Part of the CodeBreaK 101 master protocol
6. Intraperitoneal Irinotecan with Systemic FOLFOX-Bevacizumab:
   • Response Rate: Partial radiological response in 13 patients, complete response in 4 patients.
   • Details: Evaluated in patients with colorectal peritoneal metastases not eligible for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Median overall survival was 23.9 months.

These trials demonstrated promising efficacy in their respective phase I settings and are noteworthy for their response rates and clinical outcomes.

Here are the trials with the best results and highest response rates from the provided phase II colorectal cancer trials:

1. Cabozantinib and Durvalumab (CAMILLA CRC cohort)
   • Objective Response Rate (ORR): 27.6% (95% CI 12.7-47.2%)
   • Progression-Free Survival (PFS): 4-month PFS rate of 44.83% (95% CI 26.5-64.3%)
   • Overall Survival (OS): Median OS of 9.1 months (95% CI 5.8-20.2)
   • Details: Post-hoc analysis in patients with RAS wild type tumors showed an ORR of 50% with median PFS and OS of 6.3 and 21.5 months respectively​​.
2. Nintedanib and Capecitabine
   • Objective Response Rate (ORR): Not specified for ORR, but 18-week PFS was 42% (15/36 patients; P = .0209)
   • Progression-Free Survival (PFS): Median PFS of 3.4 months
   • Overall Survival (OS): Median OS of 8.9 months
   • Details: The combination showed superior efficacy compared to regorafenib or tipiracil hydrochloride monotherapy​​.
3. Hydroxyapatite-coated Intraperitoneal (HAI) Oxaliplatin with Systemic 5-Fluorouracil and Cetuximab
   • Objective Response Rate (ORR): 88% (95% CI 71%-96%) among evaluable patients (n=32) and 95% (95% CI 70-100%) among the 22 wild-type RAS/BRAF evaluable patients
   • Progression-Free Survival (PFS): Median PFS of 17.9 months (95% CI, 15-23)
   • Overall Survival (OS): Median OS of 46.3 months (95% CI, 40.0-not reached)
   • Details: High effectiveness in frontline treatment of unresectable colorectal liver metastases (CRLM)​​.
4. Anlotinib and Irinotecan
   • Objective Response Rate (ORR): 25.8%
   • Progression-Free Survival (PFS): Median PFS of 6.9 months (95% CI: 3.7, 9.3)
   • Overall Survival (OS): Median OS of 17.6 months (95% CI: 12.4, not evaluated)
   • Details: High disease control rate (93.5%) and manageable safety profile​​.
5. GC1118 in Combination with FOLFIRI
   • Objective Response Rate (ORR): 42.5% (95% CI, 23.5 to 62.0)
   • Progression-Free Survival (PFS): Median PFS of 6.7 months (95% CI, 4.0-8.0)
   • Overall Survival (OS): Not specified
   • Details: Effective as a second-line therapy for recurrent/metastatic CRC​​.
6. Sintilimab and Chidamide with/without Bevacizumab
   • Objective Response Rate (ORR): 29.2% (14 of 48)
   • Progression-Free Survival (PFS): Median PFS of 3.7 months
   • Overall Survival (OS): Median OS not mature
   • Details: Promising results in chemotherapy-refractory MSS/pMMR colorectal cancer​​.

These trials have shown significant response rates and overall positive results in the treatment of colorectal cancer.