Colon CancerPhase 2NCT03442569
PhII Trial Panitumumab, Nivolumab, Ipilimumab in Kras/Nras/BRAF Wild-type MSS Refractory mCRC
A Phase 2 study testing Panitumumab, Nivolumab and Ipilimumab in people with Colon Cancer, run by UNC Lineberger Comprehensive Cancer Center at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Colon Cancer
- What is being tested?
- Panitumumab, Nivolumab and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 5 sitesUnited States
- Study dates
- 9 Mar 2018to 2 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
- Treatment within 21 days of the first dose of study drug with any other chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment for the treatment of malignancy, or failure to recover from adverse effects of prior therapies administered over 4 weeks prior to Study Day 1. All toxicities from prior therapies must be ≤ Grade 1 (or ≤ Grade 2 for alopecia or peripheral neuropathy). Prior systemic treatment in the adjuvant setting is allowed. See note above under inclusion 3.1.8
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27509
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
University of Washington - Seattle Cancer Care Alliance
Seattle, Washington, 98109
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: Phase II Multicenter Trial of Panitumumab, Nivolumab, and Ipilimumab for KRAS/NRAS/BRAF Wild-type MSS Refractory Metastatic Colorectal Adenocarcinoma
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.
Read the detailed description
The investigators will conduct a single-arm, open-label Phase II clinical trial investigating the combination of nivolumab and ipilimumab with panitumumab in subjects with unresectable, refractory, KRAS/NRAS/BRAF wild-type, microsatellite stable (MSS) metastatic colorectal cancer (mCRC). There will be an initial safety lead-in cohort to ensure the combination is well-tolerated. The primary objective of this study is to estimate the overall response rate in these subjects at 12 weeks . Secondary objectives include the following: estimating the overall response rate in these subjects at 12 weeks by immune-related RECIST criteria (irRECIST), estimating the best response rate by both RECIST 1.1 and irRECIST criteria, estimating progression-free survival (PFS) and duration of response using both RECIST 1.1 and irRECIST criteria, estimating overall survival (OS), and characterizing the safety issues associated with this regimen. Exploratory objectives involve investigating various biomarkers and peripheral blood and tumor assays.
- Conditions
- Colon Cancer
- Being tested
- Panitumumab, Nivolumab, Ipilimumab
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanitumumabDrug
Also called Vectibix
6 mg/kg via IV every 2 weeks in combination with nivolumab and ipilimumab
NivolumabDrug
Also called Opdivo
240 mg via IV every 2 weeks in combination with panitumumab and ipilimumab
IpilimumabDrug
Also called Yervoy
1 mg/kg via IV every 6 weeks in combination with nivolumab and panitumumab
| Study group | Role | What they receive |
|---|---|---|
| Open-label, single arm, Phase II | Experimental | Nivolumab and ipilimumab with panitumumab Receives: Drug: Panitumumab; Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks
Secondary outcomes (5)
Overall Response Rate Per irRECIST
Overall Response Rate (ORR) = irCR + irPR Per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) for target and/or non-target lesions and assessed by imaging: Complete Response (irCR), Disappearance of all lesions, no new lesions, lymph nodes < 10 mm in short axis; Partial Response (irPR), ≥30% decrease in the sum of target lesions and non-target lesions are irNN; Stable response (irSD), not meeting criteria for irCR, irPR, or irPD; Progressive Disease (irPD), ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir; for no new non-target or (irNN) and where irPR or irPD are confirmed by a repeat, consecutive assessment no less than 4 weeks later
Measured: 12 weeks
Median Progression Free Survival
Median Progression Free Survival is the time at which 50% of the study population has experienced disease progression as defined by RECIST, irRECIST, or death from any cause.
Measured: Up to 3 years
Median Overall Survival
Time from the first day of treatment until death from any cause.
Measured: Up to 3 years
Median Duration of Response
Duration of response is the time from documentation of tumor response to disease progression.
Measured: Up to 3 years
Toxicity of Treatment
The number of treatment-emergent grade 3 and 4 toxicities as defined by the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03) was reported.
Measured: Up to 36 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2018
- Study start9 Mar 2018
- Primary completion21 Sep 2020
- Study completion2 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Hanna K Sanoff, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03442569
- Sponsor's protocol ID
- LCCC1632
- Status last verified
- Jun 2025
- First submitted
- 14 Feb 2018
- Last updated
- 1 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Multicenter Trial of Panitumumab, Nivolumab, and Ipilimumab for KRAS/NRAS/BRAF Wild-type MSS Refractory Metastatic Colorectal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT03442569
- Acronym / sponsor ID
- LCCC1632
- Conditions
- Colon Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Amgen, Bristol-Myers Squibb
- Study start
- 9 Mar 2018 (actual)
- Primary completion
- 21 Sep 2020 (actual)
- Study completion
- 2 Dec 2024 (actual)
- First posted
- 22 Feb 2018 (actual)
- Results
- Posted 22 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The investigators will conduct a single-arm, open-label Phase II clinical trial investigating the combination of nivolumab and ipilimumab with panitumumab in subjects with unresectable, refractory, KRAS/NRAS/BRAF wild-type, microsatellite stable (MSS) metastatic colorectal cancer (mCRC). There will be an initial safety lead-in cohort to ensure the combination is well-tolerated. The primary objective of this study is to estimate the overall response rate in these subjects at 12 weeks . Secondary objectives include the following: estimating the overall response rate in these subjects at 12 weeks by immune-related RECIST criteria (irRECIST), estimating the best response rate by both RECIST 1.1 and irRECIST criteria, estimating progression-free survival (PFS) and duration of response using both RECIST 1.1 and irRECIST criteria, estimating overall survival (OS), and characterizing the safety issues associated with this regimen. Exploratory objectives involve investigating various biomarkers and peripheral blood and tumor assays.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Open-label, single arm, Phase II | Experimental | Drug: Panitumumab, Drug: Nivolumab, Drug: IpilimumabNivolumab and ipilimumab with panitumumab |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanitumumabAlso: Vectibix6 mg/kg via IV every 2 weeks in combination with nivolumab and ipilimumab | Drug | Open-label, single arm, Phase II |
| NivolumabAlso: Opdivo240 mg via IV every 2 weeks in combination with panitumumab and ipilimumab | Drug | Open-label, single arm, Phase II |
| IpilimumabAlso: Yervoy1 mg/kg via IV every 6 weeks in combination with nivolumab and panitumumab | Drug | Open-label, single arm, Phase II |
Primary outcome
Overall Response Rate
Time frame: 12 weeks
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
5 secondary outcomes
Overall Response Rate Per irRECIST
Time frame: 12 weeks
Median Progression Free Survival
Time frame: Up to 3 years
Median Overall Survival
Time frame: Up to 3 years
Median Duration of Response
Time frame: Up to 3 years
Toxicity of Treatment
Time frame: Up to 36 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of North Carolina Lineberger Comprehensive Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hanna K Sanoff, MD principal investigator
University of North Carolina, Chapel Hill
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Panitumumab, Nivolumab and Ipilimumab in people with Colon Cancer, run by UNC Lineberger Comprehensive Cancer Center at 5 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 15 inclusion and 15 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 1 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
Yes. Results are posted in the registry (first posted 22 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jul 2025; AzTrials last refreshed its copy on 8 Nov 2026.