INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer

NCT04130854 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: STU-2019-14925R01CA283953-03
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Locally Advanced Rectal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response Rate

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

  At time of surgery

Secondary Outcomes (3)

• Overall Survival

  3 years

• Toxicity analysis

  3 years

• Disease free survival

  3 years

Other Outcomes (1)

• Exploratory Immunological Response

  3 years

Study Arms (2)

APX005M on day 3 of RT & day 3 of cycles 1-5 of mFOLFOX

EXPERIMENTAL

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.

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

Radiation Therapy 5Gy x 5 days, mFOLFOX

ACTIVE COMPARATOR

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.

Drug: mFOLFOX and Radiation Therapy 5Gy x 5 days

Interventions

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

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 on day 3 of RT & day 3 of cycles 1-5 of mFOLFOX

mFOLFOX and Radiation Therapy 5Gy x 5 days DRUG

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

Radiation Therapy 5Gy x 5 days, mFOLFOX

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age. Both men and women and members of all races and ethnic groups will be included.
• Willing and able to provide written informed consent
• Pathologic diagnosis of rectal adenocarcinoma
• Stage III or Stage II with at least 1 of the following high-risk features:
• Distal (\<1cm from anal ring)
• cT4 or within 3mm of MR fascia
• Not candidate for sphincter preservation
• Extramural venous invasion
• No prior treatment for rectal adenocarcinoma
• Eastern Cooperative Group (ECOG) performance status of 0-1.
• Laboratory values supporting acceptable organ and marrow function within 21 days of eligibility confirmation. Defined as follows:
• WBC ≥ 3,000/mL;
• ANC WBC ≥ 1,500/mL;
• PLT ≥ 100,000/mL;
• T Bili ≤ 1.5 x upper limit of normal (ULN);

You may not qualify if:

• Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT or PET
• Prior RT to the pelvis.
• Uncontrolled comorbid illness or condition including an active infection, congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements.
• Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Any positive history for HIV/AIDS, HTLV, hepatitis B or hepatitis C virus indicating acute or chronic infection.
• Any active known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the absence of active autoimmune disease.
• Malignancy in the past 3 years that required active treatment except locally curable cancers or cancers deemed by the treating physicians to not impact the subject's survival duration.
• Participants receiving any other investigational agent, standard antineoplastic agents, or immunosuppressive agents.
• Known history of interstitial lung disease.
• Received live vaccine within 6 weeks prior to randomization.
• Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
• Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Patient is not a candidate for the full treatment regimen.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• University of Texas Southwestern Medical Center: lead
• Apexigen America, Inc.: collaborator

Study Sites (4)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Wake Forest Baptist Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75390, United States

Location

MeSH Terms

Interventions

sotigalimab

Study Officials

• Todd Aguilera, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 18, 2019
• Study Start: April 24, 2020
• Primary Completion: January 30, 2026
• Study Completion: January 30, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)