PhII Trial Panitumumab, Nivolumab, Ipilimumab in Kras/Nras/BRAF Wild-type MSS Refractory mCRC

NCT03442569 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: LCCC1632
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 5

Brief Summary

To investigate the combination of nivolumab and ipilimumab with panitumumab in subjects with unresectable, refractory, KRAS/NRAS/BRAF wild-type, microsatellite stable (MSS) metastatic colorectal cancer.

Conditions

Colon Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall Response Rate (ORR) = CR + PR Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions

  12 weeks

Secondary Outcomes (5)

• Overall Response Rate Per irRECIST

  12 weeks

• Median Progression Free Survival

  Up to 3 years

• Median Overall Survival

  Up to 3 years

• Median Duration of Response

  Up to 3 years

• Toxicity of Treatment

  Up to 36 month

Study Arms (1)

Open-label, single arm, Phase II

EXPERIMENTAL

Nivolumab and ipilimumab with panitumumab

Drug: Panitumumab; Drug: Nivolumab; Drug: Ipilimumab

Interventions

Panitumumab DRUG

6 mg/kg via IV every 2 weeks in combination with nivolumab and ipilimumab

Also known as: Vectibix

Open-label, single arm, Phase II

Nivolumab DRUG

240 mg via IV every 2 weeks in combination with panitumumab and ipilimumab

Also known as: Opdivo

Open-label, single arm, Phase II

Ipilimumab DRUG

1 mg/kg via IV every 6 weeks in combination with nivolumab and panitumumab

Also known as: Yervoy

Open-label, single arm, Phase II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed colorectal adenocarcinoma, with unresectable metastatic or locally advanced disease documented on diagnostic imaging studies.
• Previously received 1-2 prior lines of therapy. Subjects who relapse within 6 months of adjuvant chemotherapy comprised of oxaliplatin and a fluoropyrimidine will have their adjuvant therapy count as one prior line of therapy.
• Confirmed wild-type in KRAS and NRAS codons 12, 13, 59, 61, 117, and 146; and BRAF codon 600, by standard of care testing of tumor specimen. Tissue used for testing may have been collected from primary or metastatic site.
• Microsatellite stable as detected by PCR-based assay or CLIA-certified sequencing methodology such as Foundation One; or mismatch repair proficient as detected by immunohistochemistry showing intact nuclear staining of MLH1, MSH2, MSH6, and PMS2
• Radiographically measurable disease present per RECIST 1.1
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Blood counts performed within 3 weeks prior to starting study therapy must have absolute neutrophil count ≥ 1,500/mm3, platelets ≥ 100,000/mm3, and hemoglobin ≥ 9 g/dL.
• \*Note: Hematology and other lab parameters that are ≤ grade 2 but still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
• Liver function tests performed within 3 weeks prior to starting study therapy must have total bilirubin ≤ 1.5 x upper limit of normal (ULN), alanine aminotransferase and aspartate aminotransferase ≤ 3 x ULN, and albumin ≥ 2.5 g/dL.
• Serum creatinine performed within 3 weeks prior to starting study therapy must be ≤ 1.5 x ULN, or have calculated creatinine clearance (using Cockcroft-Gault formula provided in Appendix 11.3) of ≥ 50 mL/minute.
• Females of childbearing potential must have a negative serum pregnancy test within 24 hours prior to receiving the first dose of study medication. Females of childbearing potential must agree to use 2 methods of effective contraception or abstain from heterosexual sex throughout the treatment period and for 5 months after the last dose of study treatment. Females of childbearing potential are women who have not been surgically sterilized (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or have not been free of menses for \>1 year.
• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 7 months after the last dose of study treatment.
• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• An adequate amount of archival tumor tissue must be available at baseline to be eligible for enrollment in the study. If archival tissue is not available or is inadequate, then the subject must consent to undergo a mandatory biopsy at baseline in order to participate in the study.

You may not qualify if:

• Past treatment with an antibody targeting EGFR including cetuximab or panitumumab.
• Past treatment with an antibody targeting immune checkpoints including CTLA-4, PD-1, PD-L1, PD-L2, or CD137.
• Known untreated brain metastasis or brain metastasis treated within 3 months prior to enrollment in this trial.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease free for at least five years.
• Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent, or compliance to the study procedures.
• Pregnant or breastfeeding, or planning to become pregnant within 6 months after the end of treatment. (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• History of organ allograft or other history of immunodeficiency, or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of investigational treatment.
• Inability or unwillingness to comply with study and/or follow-up requirements.
• Any major surgery, extensive radiotherapy, chemotherapy with clinically significant delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to randomization and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to randomization.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug.
• Known Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV) infection. Subjects with laboratory evidence of cleared HBV and HCV infection will be permitted.
• Active autoimmune disease requiring systemic treatment in the past 3 months (for example with disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, local steroid injections, or inhaled or topical steroids would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
• Active infection requiring intravenous systemic therapy.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Amgen: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (5)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27509, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Panitumumab; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Robin V. Johnson
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

robin_v_johnson@med.unc.edu

919-966-1125

Study Officials

• Hanna K Sanoff, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a single-arm, open-label, multicenter Phase II clinical trial investigating the clinical efficacy of nivolumab, ipilimumab, and panitumumab in subjects with unresectable refractory KRAS/NRAS/BRAF wild-type microsatellite stable metastatic colorectal cancer after an initial safety lead-in cohort to ensure the three drug combination is well-tolerated.

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 22, 2018
• Study Start: March 9, 2018
• Primary Completion: September 21, 2020
• Study Completion: December 2, 2024
• Last Updated: July 1, 2025
• Results First Posted: October 22, 2021

Record last verified: 2025-06

Locations

US (5)