• IGM-8447 is a second generation anti-DR5 IgM antibody agonist.

In this study, the sponsor and investigators want to learn:

• How much of the study drug can be given with an acceptable level of side effects
• The effects of the study drug (good and bad)
• How much of the study drug is absorbed into the blood and how fast it is removed
• How the study drug is acting on your body
• If research tests can be used in the future to predict who will benefit from IGM-8447

This study has 3 parts:

1. Screening (to see if you are eligible for the study)
2. Study Treatment
3. Follow-up (to check on you after study treatment is finished)

During the dose escalation stage, you will be enrolled in one of the following study treatment groups depending on what type of cancer you have:

• Single agent dose-escalation group will enroll all types of solid tumor cancers and you may receive one of the 6 different IGM-8447 doses starting from a low dose. IGM-8447 will be given alone as an infusion into the vein on Day 1 and Day 15 of each cycle for up to 13 cycles. Each cycle is 28 days long.
• Combination dose-escalation group will enroll only colon or rectal cancers and you may receive 1 of 4 different IGM-8447 doses that have been shown to be safe in the single agent dose-escalation group, in combination with FOLFIRI + bevacizumab by infusion. IGM-8447 will be given as an infusion into the vein on Day 1 and Day 15 of each cycle for up to 13 cycles. Each cycle is 28 days long.

During the dose expansion stage, colon or rectal cancers will be the focus and you will be enrolled to receive IGM-8447 in combination with FOLFIRI + bevacizumab. IGM 8447 will be given as an infusion into the vein on Day 1 and Day 15 of each cycle for up to 13 cycles. Each cycle is 28 days long.

You will be asked to take IGM-8447 alone or in combination with FOLFIRI and bevacizumab until your cancer worsens. After your last dose, your study doctor will follow up with you in about 1 month. Your total time in the study will depend on how your cancer responds to study treatment. This could range from 1 day to more than 12 months.