MelanomaPhase 1/2NCT03580382
Study of CDX-3379, a Human Monoclonal Antibody Targeting ERBB3, in Combination With the MEK Inhibitor, Trametinib, in Patients With Advanced Stage NRAS Mutant and BRAF/NRAS Wildtype (WT) Melanoma
A Phase 1/2 study testing Trametinib daily Until PD and CDX-3379 (ERBB3 antibody) in people with Melanoma, run by NYU Langone Health at 2 sites in United States.
Trial summary
The main goal of this study is to test if it is safe and effective to give CDX-3379 together to treat advanced melanoma in patients with the NRAS mutation and BRAF/NRAS wildtype. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Trametinib daily Until PD and CDX-3379 (ERBB3 antibody)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Jul 2018to 26 Sep 2018
- Phase
- Phase 1/2
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Read, understood, and provided written informed consent and, if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures.
- 2. Male or female patients who are 18 years of age or older. 3. Patients with a diagnosis of histologically confirmed advanced (defined as unresectable stage III or IV) melanoma with the NRAS Q61 mutation or BRAF/NRAS WT for which there is no remaining standard therapy with curative potential or patients are ineligible or unable to tolerate therapy with curative potential.
- Any standard of care mutation testing is acceptable to document mutation status.
- 4.Patients must have archival tissue and at least one disease site amenable to biopsy:
- For phase Ib, all patients will undergo fresh tumor biopsy
- For phase II, five patients with NRAS mutation and five patients with BRAF/NRAS WT melanoma will undergo fresh tumor biopsy 5.Measurable (target) disease by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Target lesions selected for tumor measurements should be those where additional (eg palliative) treatments are not indicated or anticipated.
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- Measurable disease per RECIST 1.1 requirements: defined as longest diameter to be recorded for non-nodal lesions > 10mm and short axis for nodal lesions >15 mm using conventional techniques 6.All residual toxicity related to prior radiotherapy or anticancer therapies (excluding alopecia, grade 2 fatigue, vitiligo or endocrinopathies on stable replacement therapy) must resolve to grade 1 severity or less (or returned to baseline) prior to receipt of study treatment.
- 7.Adequate electrolytes, liver, renal, and hematology function as defined below:
- a.Hemoglobin ≥ 9 g/dL b.Absolute neutrophil count ≥ 1500/mm3 c.Platelet count ≥ 100,000/mm3 d.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) (≤ 5 × ULN for cases involving liver metastasis) e.Bilirubin ≤ 1.5 × ULN (≤ 5 × ULN for cases of documented or suspected Gilbert's disease) f.Serum creatinine ≤ 1.5 g/dL or calculated creatinine clearance (CrCl) ≥60 mL/min for patients with serum creatinine > 1.5 x ULN g.Serum magnesium, calcium and potassium within normal limits 8.Life expectancy ≥ 12 weeks 9.ECOG performance status (PS) < 1 10.Willing and able to comply with scheduled visits, treatment plan, and laboratory tests.
- 11.Screening EKG without clinically significant abnormalities. 12.Corrected (Fridericia's) QTcF must be < 480 milliseconds. 13.Allowance of prior therapy regimens:
- No limit on prior number of regimens
- Must have completed prior cytotoxic chemotherapy a minimum of 4 weeks prior to starting study treatment (except for bis-chlorethynitrosurea (BCNU)), which must have been completed a minimum of 6 weeks prior to starting therapy.
- Prior localized radiation therapy must have been completed a minimum of 2 weeks prior to starting therapy and the patient must have baseline imaging with a full body PET-CT or CT scans of the chest, abdomen, and pelvis and within 4 weeks prior to study enrollment.
- For CNS metastases, disease must be treated and demonstrate stability with Brain MRI a minimum of 2 weeks prior to starting therapy.
- 14.Both male and female patients enrolled in this trial must agree to use highly effective contraception during the course of the trial and for at least for 6 months after the final dose of CDX-3379 (an effective form of contraception is an oral contraceptive or a double barrier method), or greater, as in accordance with the label requirements for trametinib. Patients and/or partners who are surgically sterile or postmenopausal are exempt from this requirement.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after stopping study drug. Highly effective contraception methods include:
- Total abstinence or
- Male or female sterilization or
- Combination of any two of the following (a+b or a+c or b+c):
- Use of oral, injected or implanted hormonal methods of contraception; hormonal contraceptives are not acceptable as a sole method of contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository 15. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
Who cannot join
- Received CDX-3379 or other anti-ErbB3 targeted agents previously.
- Received trametinib or other MEK inhibitor agents previously.
- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
- Other prior malignancy active within 2 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast that has/have undergone curative surgery or radiation.
- Active central nervous system (CNS) metastases are excluded. Known brain metastases must have been previously treated and asymptomatic for 2 weeks and not progressive in size or number for 4 weeks prior to enrollment, documented via scans. Continued use of anticonvulsants (in the absence of any suspicion of progressive brain metastases) is acceptable. Patients must currently be on a stable, lowest possible dose of steroids.
- Radiation therapy within 14 days prior to the first scheduled dose in this study, including, in addition (if necessary), the timeframe for resolution of any actual or anticipated toxicities from such radiation.
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- Known HIV, hepatitis B or hepatitis C infection, or active infection requiring systemic intravenous therapy
- Use of any monoclonal based therapies within 4 weeks (excluding cetuximab which does not require a wash-out), and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks, prior to the first dose of study treatment.
- Chemotherapy within 4 weeks (except for bis-chlorethynitrosurea (BCNU), which must have been completed a minimum of 6 weeks) prior to starting therapy.
- Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.
- Use of other investigational drugs within 2 weeks or 5 half-lives (whichever is longer) prior to study treatment administration
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms); additional risk factors for torsades de pointes (TdP) (e.g., a history of heart failure, family history of Long QT Syndrome, or active hypokalemia or uncorrectable electrolyte abnormality); significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, congestive heart failure (New York Heart Association Class III or IV) related to primary cardiac disease, uncontrolled ischemic or severe valvular heart disease; or any of the following within 6 months prior to the first dose of study treatment: myocardial infarction, severe/unstable angina, coronary artery bypass graft, congestive heart failure, cerebrovascular accident, transient ischemic attack.
- Requirement for chronic immunosuppressive medication including systemic corticosteroids above the physiologic dose (defined as 20 mg/day prednisone or the equivalent).
- Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.
- Known alcohol or drug abuse.
- Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
- Inability to swallow pills
- Patients unwilling or unable to comply with the protocol.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
New York University School of Medicine
New York, New York, 10016
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
The main goal of this study is to test if it is safe and effective to give CDX-3379 together to treat advanced melanoma in patients with the NRAS mutation and BRAF/NRAS wildtype.
Read the detailed description
Primary Objectives:
Phase 1b: To determine the RP2D and assess the toxicity and tolerability of the combination of CDX-3379 (ERBB3 antibody) and trametinib (MEK inhibitor) in NRAS and BRAF/NRAS WT melanoma patients
Phase 2: To estimate the response rates and duration of response of the combination of CDX-3379 (ERBB3 antibody) and trametinib in NRAS positive and BRAF/NRAS WT melanoma patients
Secondary/Exploratory Objectives:
Phase 1b: To assess clinical activity and steady-state pharmacokinetics of CDX-3379 and trametinib Phase 2: To compare the efficacy of the combination of CDX-3379 (ERBB3 antibody) and trametinib is more effective than a MEK inhibitor alone in NRAS positive and BRAF/NRAS WT melanoma patients alone using locally assessed progression free survival (PFS) and overall survival (OS).
- Conditions
- Melanoma
- Being tested
- Trametinib daily Until PD, CDX-3379 (ERBB3 antibody)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trametinib daily Until PDDrug
1.0 mg daily
CDX-3379 (ERBB3 antibody)Drug
15mg/kg IV Q3W
| Study group | Role | What they receive |
|---|---|---|
| NRAS mutant melanoma | Experimental | C1D1-C1D21, CDX-3379 D1Trametinib daily Biopsy (days 14-16) Receives: Drug: Trametinib daily Until PD; Drug: CDX-3379 (ERBB3 antibody) |
| WT melanoma | Experimental | C1D1-C1D21, CDX-3379 D1Trametinib daily Biopsy (days 14-16) Receives: Drug: Trametinib daily Until PD; Drug: CDX-3379 (ERBB3 antibody) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
response rate, will be compared with the historically reported response rate for the single agent trametinib in NRAS and BRAF/NRAS WT melenoma
Measured: 48 Months
Overall Survival (OS)
Survival data will be collectedvia telephone or clinic visits every 3 months (+10 days) from the date of last treatment, and median will be estimated using Kaplan-Meier approach
Measured: 48 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2018
- Study start6 Jul 2018
- Primary completion26 Sep 2018
- Study completion26 Sep 2018
Why it stopped: Per regulatory coordinator, the sponsor is no longer supporting the study.
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 MelanomaStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Celldex Therapeutics
- Responsible party
- Sponsor
- Investigators
- Jeffrey Weber, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03580382
- Sponsor's protocol ID
- 17-00363
- Status last verified
- May 2020
- First submitted
- 5 Jul 2018
- Last updated
- 20 May 2020
- 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 20 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of CDX-3379, a Human Monoclonal Antibody Targeting ERBB3, in Combination With the MEK Inhibitor, Trametinib, in Patients With Advanced Stage NRAS Mutant and BRAF/NRAS Wildtype (WT) Melanoma
- ClinicalTrials.gov ID
- NCT03580382
- Acronym / sponsor ID
- 17-00363
- Conditions
- Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Per regulatory coordinator, the sponsor is no longer supporting the study.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- Celldex Therapeutics
- Study start
- 6 Jul 2018 (actual)
- Primary completion
- 26 Sep 2018 (actual)
- Study completion
- 26 Sep 2018 (actual)
- First posted
- 9 Jul 2018 (actual)
- Results
- Posted 20 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main goal of this study is to test if it is safe and effective to give CDX-3379 together to treat advanced melanoma in patients with the NRAS mutation and BRAF/NRAS wildtype.
Detailed description
Primary Objectives:
Phase 1b: To determine the RP2D and assess the toxicity and tolerability of the combination of CDX-3379 (ERBB3 antibody) and trametinib (MEK inhibitor) in NRAS and BRAF/NRAS WT melanoma patients
Phase 2: To estimate the response rates and duration of response of the combination of CDX-3379 (ERBB3 antibody) and trametinib in NRAS positive and BRAF/NRAS WT melanoma patients
Secondary/Exploratory Objectives:
Phase 1b: To assess clinical activity and steady-state pharmacokinetics of CDX-3379 and trametinib Phase 2: To compare the efficacy of the combination of CDX-3379 (ERBB3 antibody) and trametinib is more effective than a MEK inhibitor alone in NRAS positive and BRAF/NRAS WT melanoma patients alone using locally assessed progression free survival (PFS) and overall survival (OS).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NRAS mutant melanoma | Experimental | Drug: Trametinib daily Until PD, Drug: CDX-3379 (ERBB3 antibody)C1D1-C1D21, CDX-3379 D1Trametinib daily Biopsy (days 14-16) |
| WT melanoma | Experimental | Drug: Trametinib daily Until PD, Drug: CDX-3379 (ERBB3 antibody)C1D1-C1D21, CDX-3379 D1Trametinib daily Biopsy (days 14-16) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 1. Read, understood, and provided written informed consent and, if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures.
- 2. Male or female patients who are 18 years of age or older. 3. Patients with a diagnosis of histologically confirmed advanced (defined as unresectable stage III or IV) melanoma with the NRAS Q61 mutation or BRAF/NRAS WT for which there is no remaining standard therapy with curative potential or patients are ineligible or unable to tolerate therapy with curative potential.
- a.Hemoglobin ≥ 9 g/dL b.Absolute neutrophil count ≥ 1500/mm3 c.Platelet count ≥ 100,000/mm3 d.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) (≤ 5 × ULN for cases involving liver metastasis) e.Bilirubin ≤ 1.5 × ULN (≤ 5 × ULN for cases of documented or suspected Gilbert's disease) f.Serum creatinine ≤ 1.5 g/dL or calculated creatinine clearance (CrCl) ≥60 mL/min for patients with serum creatinine > 1.5 x ULN g.Serum magnesium, calcium and potassium within normal limits 8.Life expectancy ≥ 12 weeks 9.ECOG performance status (PS) < 1 10.Willing and able to comply with scheduled visits, treatment plan, and laboratory tests.
- 11.Screening EKG without clinically significant abnormalities. 12.Corrected (Fridericia's) QTcF must be < 480 milliseconds. 13.Allowance of prior therapy regimens:
- 14.Both male and female patients enrolled in this trial must agree to use highly effective contraception during the course of the trial and for at least for 6 months after the final dose of CDX-3379 (an effective form of contraception is an oral contraceptive or a double barrier method), or greater, as in accordance with the label requirements for trametinib. Patients and/or partners who are surgically sterile or postmenopausal are exempt from this requirement.
Key exclusion criteria (18 listed)
- Received CDX-3379 or other anti-ErbB3 targeted agents previously.
- Received trametinib or other MEK inhibitor agents previously.
- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
- Other prior malignancy active within 2 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast that has/have undergone curative surgery or radiation.
- Active central nervous system (CNS) metastases are excluded. Known brain metastases must have been previously treated and asymptomatic for 2 weeks and not progressive in size or number for 4 weeks prior to enrollment, documented via scans. Continued use of anticonvulsants (in the absence of any suspicion of progressive brain metastases) is acceptable. Patients must currently be on a stable, lowest possible dose of steroids.
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 |
|---|---|---|
| Trametinib daily Until PD1.0 mg daily | Drug | NRAS mutant melanoma, WT melanoma |
| CDX-3379 (ERBB3 antibody)15mg/kg IV Q3W | Drug | NRAS mutant melanoma, WT melanoma |
Primary outcome
Objective Response Rate
Time frame: 48 Months
response rate, will be compared with the historically reported response rate for the single agent trametinib in NRAS and BRAF/NRAS WT melenoma
Overall Survival (OS)
Time frame: 48 Months
Survival data will be collectedvia telephone or clinic visits every 3 months (+10 days) from the date of last treatment, and median will be estimated using Kaplan-Meier approach
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jeffrey Weber, MD principal investigator
NYU Langone Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Trametinib daily Until PD and CDX-3379 (ERBB3 antibody) in people with Melanoma, run by NYU Langone Health at 2 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 22 inclusion and 18 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: stopped early, as of the sponsor's last update on 20 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 20 May 2020). 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?
Objective Response Rate (time frame: 48 Months). The study lists 2 primary outcomes in all. 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 20 May 2020.