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On Day 3 of Cycles 1-5 of each mFOLFOX treatment, participants will receive another dose of APX005M. The sequence of administration of APX005M in combination with mFOLFOX. In Cycle 6, participants will receive only mFOLFOX. After completing the last planned dose of mFOLFOX, participants will be considered off-protocol directed therapy and undergo planned TME, per institutional standards, and proceed to the follow-up portion of this study.

Participants randomized to Arm 2 will receive short-course RT and mFOLFOX regimen, except that participants will not receive any of the study drug. After completing the last planned dose of mFOLFOX, participants will be considered off-protocol directed therapy and undergo planned TME, per institutional standards, and proceed to the follow-up portion of this study.

1. APX005M 0.3mg/kg intravenously on day 3 of radiation and on day 3 of cycles 1-5 of mFOLFOX
2. Short course radiation therapy 5 Gy x 5 days
3. Oxaliplatin 85mg/m2 intravenous day 1 of each cycle
4. Leucovorin 400mg/m2 IV Day 1 of each cycle
5. 5-FU 2400 mg/m2 continuous infusion over 46 hours of each cycle

APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days

1. Short course radiation therapy 5 Gy x 5 days
2. Oxaliplatin 85mg/m2 intravenous day 1 of each cycle
3. Leucovorin 400mg/m2 IV Day 1 of each cycle
4. 5-FU 2400 mg/m2 continuous infusion over 46 hours of each cycle

mFOLFOX and Radiation Therapy 5Gy x 5 days

Todd Aguilera, MD

Determine the complete pathologic complete response (pCR) rate in patients with locally advanced rectal adenocarcinoma.

A phase II randomized trial 3:2 with short course radiotherapy followed by mFOLFOX chemotherapy prior to trans abdominal resection with or without an antiCD40 agonist antibody (APX005M). There will be continuous safety assessment for at least 6 patients. Planned accrual of 58 patients. An interim analysis after 30 patients have completed treatment and there will be early stopping criteria for futility or efficacy. Short course radiotherapy will consist of 5Gy x 5 to the pelvis and patients on APX005M arm will receive one infusion during radiotherapy course, have a two week break, then start FOLFOX with APX005M in conjunction with five out of six cycles of chemotherapy. Patients will be restaged and then undergo definitive surgery.

INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer

INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer, a Phase II Randomized Multi-center Trial With and Without APX005M, an Anti-CD40 Agonist

To evaluate the immunologic response surrogates for patients tissue is obtained.

The primary objective of this study is to determine the pathologic complete response (pCR) rate of the combined treatment modality.

To evaluate overall survival (OS), defined as the time between date of randomization and the date of death due to any cause.

To evaluate toxicity analysis comparing the experimental from the standard arm measured according to CTCAE v5.0.

To evaluate the disease free survival (DFS) and patterns of failure at three years. DFS is defined as the time between the date of definitive surgery and the first date of documented disease progression or death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer	NCT04130854	Locally Advance...	APX005M, mFOLFO... mFOLFOX and Rad...	18 Years - 99 Years	University of Texas Southwestern Medical Center
INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer	NCT04130854	Locally Advance...	APX005M, mFOLFO... mFOLFOX and Rad...	18 Years - 99 Years	University of Texas Southwestern Medical Center

Spots Global Cancer Trial Database for apx005m, mfolfox, and radiation therapy 5gy x 5 days