Lenvatinib and Pembrolizumab to Treat Patients With Anal or Rectum Cancer That Has Gotten Worse After Initial Treatment

This study tests the combination of lenvatinib (a targeted drug that cuts off tumor blood supply) plus pembrolizumab (an immunotherapy) for people with anal or rectal squamous cell carcinoma that has returned, spread, or cannot be removed with surgery, and has progressed after initial chemotherapy or chemoradiation. **You may be eligible if...** - You are 18 or older with confirmed anal or rectal squamous cell carcinoma - Your cancer has gotten worse after first-line chemotherapy or chemoradiation - Your cancer cannot be surgically removed - You have measurable tumors on scans - You are in good health (ECOG 0–1) with adequate blood and organ function **You may NOT be eligible if...** - Your cancer is a different type (not squamous cell) - Your blood counts or organ function are outside acceptable ranges - You have uncontrolled heart or kidney disease - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.