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IDO1 Inhibitor

Epacadostat + Chemoradiation for Rectal Cancer

Phase 1 & 2

Recruiting

Led By Haeseong Park, M.D., M.P.H.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Newly diagnosed locally advanced rectal cancer with pathology confirmation with plans to proceed with neoadjuvant short course radiation and chemotherapy as confirmed by treating physician

At least 18 years of age

Must not have

Receipt of live attenuated vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed

Evidence of interstitial lung disease or active, non-infectious pneumonitis including symptomatic and/or pneumonitis requiring treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through completion of follow-up (estimated to be 3 years and 32 weeks)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new cancer drug in combination with radiation and chemo for rectal cancer patients before surgery.

Who is the study for?

This trial is for adults with newly diagnosed locally advanced rectal cancer who are planning to receive neoadjuvant radiation and chemotherapy. Participants must be in good physical condition (ECOG ≤ 1), have normal organ and bone marrow function, agree to use contraception, and not have had previous cancer treatments or certain other medical conditions.

What is being tested?

The study tests epacadostat combined with CAPOX chemotherapy and short-course radiation before surgery for rectal cancer. It aims to see if this combination improves outcomes compared to the standard preoperative treatment.

What are the potential side effects?

Potential side effects may include immune-related reactions due to epacadostat, digestive issues from chemotherapy, fatigue, blood cell count changes leading to increased infection risk or bleeding problems, liver enzyme alterations, and possible allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been newly diagnosed with advanced rectal cancer and will undergo radiation and chemotherapy.

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I am 18 years old or older.

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I am fully active and can carry on all my pre-disease activities without restriction.

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My kidney function is within the normal range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not received any live vaccines in the last 30 days.

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I do not have lung inflammation or disease that needed treatment.

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I have had treatment for rectal cancer before.

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My tumor has grown into the upper part of my sacrum or nerve roots, making surgery impossible.

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My cancer has spread or my rectal tumor has come back.

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I have had allergic reactions to certain cancer drugs before.

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I am currently being treated for an infection.

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I have had serotonin syndrome from certain medications before.

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I do not have any uncontrolled illnesses like heart failure or irregular heartbeat.

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I have active tuberculosis.

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I have an active hepatitis B or C infection confirmed by tests.

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My rectal cancer is MSI-H or has mismatch repair deficiency.

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I have been diagnosed with FAP, HNPCC, Crohn's disease, or ulcerative colitis.

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I have previously been treated with specific immune-targeting cancer drugs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through completion of follow-up (estimated to be 3 years and 32 weeks)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through completion of follow-up (estimated to be 3 years and 32 weeks)

This trial's timeline: 3 weeks for screening, Varies for treatment, and through completion of follow-up (estimated to be 3 years and 32 weeks) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase I only: Recommended phase II dose (RP2D) of epacadostat with standard of care radiation and chemotherapy in preoperative treatment of locally advanced rectal cancer

Phase II Treatment Cohort only: Neoadjuvant Rectal (NAR) Score

Secondary study objectives

Phase I and Phase II Treatment Cohort only: Complete clinical response rate (cCR)

Phase I and Phase II Treatment Cohort only: Pathological complete response rate (pCR)

Phase I and Phase II Treatment Cohort only: Progression-free survival (PFS)

+2 more

Side effects data

From 2020 Phase 3 trial • 93 Patients • NCT03361865

33%

Anaemia

23%

Diarrhoea

23%

Rash

23%

Pruritus

21%

Asthenia

19%

Malignant neoplasm progression

16%

Back pain

16%

Constipation

14%

Nausea

14%

Fatigue

12%

Dyspnoea

12%

Blood creatinine increased

12%

Decreased appetite

12%

Hypoalbuminaemia

12%

Urinary tract infection

12%

Pyrexia

Amylase increased

Aspartate aminotransferase increased

Cough

Hypocalcaemia

Lipase increased

Pneumonitis

Haematuria

Vomiting

Alanine aminotransferase increased

Arthralgia

Creatinine renal clearance decreased

Dysuria

Hyperuricaemia

Insomnia

Oedema peripheral

Hyperkalaemia

Hypothyroidism

Pneumonia

Weight decreased

Abdominal pain

Urosepsis

Blood alkaline phosphatase increased

Device occlusion

Pain in extremity

Lymph gland infection

Urinary tract stoma complication

Septic shock

Encephalitis

Hepatitis

Herpes zoster

Death

Hypophysitis

Renal failure

Left ventricular dysfunction

Nephropathy toxic

Small intestinal obstruction

Somnolence

Pneumocystis jirovecii pneumonia

Renal impairment

Supraventricular tachycardia

Urticaria

Flank pain

Musculoskeletal pain

Gastroenteritis

Hypercalcaemia

Lung neoplasm malignant

Pneumothorax

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab 200 mg + Epacadostat 100 mg BID

Pembrolizumab 200 mg + Placebo BID

Total

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Phase II Treatment Cohort: Epacadostat + SCRT + Chemotherapy + SurgeryExperimental Treatment4 Interventions

* Epacadostat 400 mg BID 1st day of radiation therapy and continuing for \~28 days, until biopsy (with the exception of patients enrolling to dose expansion and starting on epacadostat with neoadjuvant chemotherapy prior to approval of post-sIRB A2) * Preoperative therapy approximately 20-24 weeks of chemoradiation: * Week 1: SCRT, typically 5 Gy x 5 fractions over 1 week, with epacadostat 400 mg BID starting on D1 of SCRT * Weeks 2-4: Epacadostat monotherapy 400 mg BID \& continued for a minimum of 21 days, until the day prior to chemotherapy * For patients enrolled at Washington University and Dana Farber Cancer Institute ONLY, tumor biopsy between the end of RT and prior to initiation of chemotherapy. Tumor biopsy target of between Days 15-28 * Weeks 3-6: 4-5 weeks after completion of SCRT \& after completion of approximately 21-35 days of epacadostat, SOC neoadjuvant chemotherapy of CAPOX or FOLFOX will be initiated * Surgery will occur approximately 4-6 weeks after chemotherapy

Group II: Dose Escalation Cohort (Phase I): Epacadostat + SCRT + Chemotherapy + SurgeryExperimental Treatment3 Interventions

* Epacadostat at the designated dose level starting on the 1st day of radiation therapy and continuing throughout chemotherapy until the day of surgery. * Standard of care preoperative therapy will consist of a total of approximately 20-24 weeks of short-course pelvic radiation and chemotherapy: * Cycle 0 Days 1-7(Week 1): Short-course pelvic radiation therapy (SCRT), 5 fractions over 1 week * Cycle 0 Days 8-21 or 8-28 (Weeks 2-4): Treatment break for 2 to 3 weeks; for patients enrolled at Washington University and Dana Farber only, tumor biopsy will be obtained between the end of RT and prior to chemotherapy (target Days 14-28) * Cycles 1-6: (6) 21-day cycles of CAPOX for a total of 18 weeks. CAPOX is typically capecitabine at 1000 mg/m\^2 PO BID (days 1-14 of each cycle) and oxaliplatin 130 mg/m\^2 IV Q3W. * Surgery will follow approximately 4 to 6 weeks after completion of CAPOX

Group III: Phase II Biomarker Cohort: SCRT + Chemotherapy + SurgeryActive Control3 Interventions

Washington University and Dana Farber only: Patients enrolled to this cohort will not receive epacadostat. Patients will undergo standard of care preoperative therapy consisting of approximately 20 to 24 weeks of chemoradiation. All treatment will be administered in this cohort as per institutional standard. The expected schedule for these patients will consist of 1 week of short-course pelvic radiation therapy, followed by a treatment break, followed by neoadjuvant chemotherapy. Approximately 4 to 6 weeks after completion of neoadjuvant chemotherapy, patients may undergo surgery. Tumor biopsy may occur at screening and after completion of RT, prior to starting neoadjuvant chemotherapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Epacadostat

2018

Completed Phase 3

~1210

0 / 18Eligibility criteria met