Pancreatic cancer – phase I/II trials of interest

Here are the phase I trials in pancreatic cancer with the best results and highest response rates based on the provided abstracts:

1. Sotorasib for KRAS p.G12C-mutated Pancreatic Cancer:
   • Objective Response Rate (ORR): 21% (8 out of 38 patients)
   • Median Progression-Free Survival (PFS): 4.0 months
   • Median Overall Survival (OS): 6.9 months
   • Safety: Treatment-related adverse events in 42% of patients, with 16% experiencing grade 3 adverse events.
   • Conclusion: Sotorasib showed anticancer activity and had an acceptable safety profile in previously treated patients​​.
2. Combination of CPI-613 and FOLFIRINOX:
   • Cohorts: 20 patients with metastatic pancreatic cancer and 60 patients with borderline-resectable pancreatic cancer treated with curative surgery.
   • Median Overall Survival (OS): 1.8 years for CPI-613 cohort versus 1.9 years for resected cases (p = 0.779)
   • Median Progression-Free Survival (PFS)/Disease-Free Survival (DFS): 1.4 years for CPI-613 versus 1.7 years for resected cases (p = 0.512)
   • Conclusion: No significant differences in survival outcomes between the cohorts. Suggests potential utility of CPI-613 with additional research needed​​.
3. Trastuzumab Deruxtecan (T-DXd) for HER2-expressing Tumors:
   • Overall Response Rate (ORR): 37.1% across all tumor types, with responses in all cohorts including pancreatic cancer
   • Median Duration of Response (DOR): 11.3 months
   • Median Progression-Free Survival (PFS): 6.9 months
   • Median Overall Survival (OS): 13.4 months
   • Conclusion: Demonstrated durable clinical benefit and meaningful survival outcomes with manageable safety profile​​.
4. Oleclumab ± Durvalumab:
   • Objective Response Rate (ORR) in Pancreatic Cancer (PDAC) Expansion Cohort: 4.8% (1 complete response, 1 partial response)
   • Safety: Manageable safety profile with treatment-related adverse events in 57% of PDAC patients
   • Conclusion: Evidence of antitumor activity observed in generally immunotherapy-resistant tumor types​​.
5. Toripalimab plus Surufatinib:
   • Objective Response Rate (ORR): 21.1% in NET cohort and 23.8% in NEC-MiNEN cohort
   • Median Duration of Response (DOR): 7.1 months in NET cohort and 4.1 months in NEC-MiNEN cohort
   • Median Progression-Free Survival (PFS): 9.6 months in NET cohort and 4.1 months in NEC-MiNEN cohort
   • Median Overall Survival (OS): 27.3 months in NET cohort and 10.9 months in NEC-MiNEN cohort
   • Conclusion: Showed tolerable safety profile and preliminary efficacy​​.

These trials highlighted notable response rates and survival outcomes, indicating promising results for specific therapies in phase I pancreatic cancer studies.

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

1. Trastuzumab deruxtecan (T-DXd) in HER2-expressing pancreatic cancer:
   • Objective Response Rate (ORR): 37.1% overall; 61.3% in HER2 IHC 3+ population
   • Median Duration of Response (DOR): 11.3 months; 22.1 months in HER2 IHC 3+ population
   • Median Progression-Free Survival (PFS): 6.9 months; 11.9 months in HER2 IHC 3+ population
   • Median Overall Survival (OS): 13.4 months; 21.1 months in HER2 IHC 3+ population
   • Conclusion: This study demonstrated durable clinical benefit, meaningful survival outcomes, and safety consistent with the known profile in pretreated patients with HER2-expressing tumors receiving T-DXd​​.
2. Combination of S-1, sintilimab, and anlotinib in pancreatic cancer with liver metastasis:
   • Objective Response Rate (ORR): 10.5%
   • Median Progression-Free Survival (PFS): 3.53 months
   • Median Overall Survival (OS): 8.53 months
   • Conclusion: This study suggests the advantage of this combination therapy in extending OS as a second-line therapy in pancreatic cancer patients with liver metastasis​​.
3. Avasopasem manganese with ablative SBRT for localized pancreatic ductal adenocarcinoma:
   • Efficacy Response: 89% at 50 Gy and 100% at 55 Gy in the avasopasem group
   • Conclusion: The avasopasem group satisfied boundaries for both efficacy and toxicity, recommending 50 Gy or 55 Gy in five fractions with avasopasem for further study​​.
4. NEPAFOX trial (perioperative FOLFIRINOX) in resectable pancreatic cancer:
   • Median RFS/PFS: 14.1 months in the perioperative FOLFIRINOX arm vs. 8.4 months in the adjuvant gemcitabine arm
   • R0-resection rate: 71% in the perioperative FOLFIRINOX arm
   • Conclusion: The perioperative treatment approach appears feasible and potentially effective in well-selected cohorts of patients​​.
5. S-1 adjuvant chemotherapy in resected pancreatic cancer:
   • 2-year Overall Survival (OS): 71.5% for 6-month therapy; 65.4% for 12-month therapy
   • 2-year Disease-Free Survival (DFS): 46.4% for 6-month therapy; 44.9% for 12-month therapy
   • Conclusion: 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS​​.
6. Reduced dose gemcitabine and nab-paclitaxel in vulnerable patients with non-resectable pancreatic cancer:
   • Primary Endpoint: Progression-free survival
   • Secondary Endpoints: Overall survival, overall response rate, quality of life, toxicity, and rate of hospitalizations
   • Conclusion: The study investigates whether reduced dose combination chemotherapy is superior to full dose gemcitabine in patients who are not candidates for full dose combination chemotherapy​​.

These abstracts highlight significant advancements and promising results in the treatment of pancreatic cancer.