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Locally Advanced Rectal AdenocarcinomaPhase 2NCT04130854

INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer

A Phase 2 study testing APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days and mFOLFOX and Radiation Therapy 5Gy x 5 days in people with Locally Advanced Rectal Adenocarcinoma, run by University of Texas Southwestern Medical Center at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Determine the complete pathologic complete response (pCR) rate in patients with locally advanced rectal adenocarcinoma. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Locally Advanced Rectal Adenocarcinoma
What is being tested?
APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days and mFOLFOX and Radiation Therapy 5Gy x 5 days
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
4 sitesUnited States
Study dates
24 Apr 2020to 30 Jan 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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);
  • AST/ALT ≤ 2.5 x ULN;
  • Creatinine ≤ 1.5 times upper limit of normal or calculated creatinine clearance > 45 mL/min per Cockcroft-Gault equation.
  • Female participants of childbearing potential (FOCBP) must have a negative serum or urine pregnancy test (per institutional standards) within 72 hours prior to the start of study drug.
  • FOCBP must agree to use highly-effective method(s) of contraception (Appendix A) during the study and for 90 days after the last dose of study drugs.
  • FOCBP are those who have not been surgically sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or have not been free from menses for >1 year without an alternative medical cause.
  • Male participants must agree to use an adequate method of contraception (Appendix A) starting with the first dose of study therapy through 90 days after the last dose of study drugs.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

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

    Dallas, Texas, 75390

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85724

  • Wake Forest Baptist Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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

Read the detailed description

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.

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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 daysDrug

    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

  • mFOLFOX and Radiation Therapy 5Gy x 5 daysDrug

    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
Study groups in NCT04130854
Study groupRoleWhat they receive
APX005M on day 3 of RT & day 3 of cycles 1-5 of mFOLFOXExperimentalOn 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.
Receives: Drug: APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days
Radiation Therapy 5Gy x 5 days, mFOLFOXActive comparatorParticipants 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.
Receives: Drug: mFOLFOX and Radiation Therapy 5Gy x 5 days

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At time of surgery

Secondary outcomes (3)

  1. Overall Survival

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

    Measured: 3 years

  2. Toxicity analysis

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

    Measured: 3 years

  3. Disease free survival

    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.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2019
  2. Study start24 Apr 2020
  3. Primary completion30 Jan 2026
  4. Study completion30 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04130854
Sponsor's protocol ID
STU-2019-1492
Other IDs
5R01CA283953-03
Status last verified
May 2026
First submitted
15 Oct 2019
Last updated
6 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zhang H, Liu J, Rajamohan N, Sanford NN, Khatri G, Rodriguez AP, Rajaram S, Jiang S, Timmerman R, Aguilera T, Peng H. Exploring radiomic and topological features to evaluate treatment response in rectal cancer. Phys Med Biol. 2025 Oct 22;70(21). doi: 10.1088/1361-6560/ae117f.

    PubMed 41067249

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days and mFOLFOX and Radiation Therapy 5Gy x 5 days in people with Locally Advanced Rectal Adenocarcinoma, run by University of Texas Southwestern Medical Center at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological Complete Response Rate (time frame: At time of surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04130854, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.

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