Preheat your oven to 375°F (190°C) and line a rimmed baking sheet with parchment paper or aluminum foil.
In a small bowl, whisk together 1/2 cup ketchup, 3 tablespoons light brown sugar, and 1 tablespoon Worcestershire sauce to create the glaze. Set aside.
In a large mixing bowl, combine the 1 cup panko breadcrumbs and 1/2 cup milk. Let it sit for 5 minutes to soften the breadcrumbs into a panade.
Add the 2 lbs ground beef, beaten eggs, diced onion, minced garlic, salt, black pepper, Italian seasoning, and 1/2 cup ketchup to the breadcrumb mixture. Gently mix with your hands until just combined; do not overmix.
Transfer the beef mixture to the prepared baking sheet and shape it into an 8x4-inch loaf.
Spread half of the prepared glaze evenly over the top and sides of the raw loaf.
Bake in the preheated oven for 40 minutes.
Remove from the oven, brush with the remaining glaze, and bake for an additional 15-20 minutes, or until the internal temperature reaches 160°F (71°C) on an instant-read thermometer.
Let the loaf rest for 10 minutes before slicing and serving.