Advanced Solid TumorsPhase 1NCT00734305
Phase I Safety Study of the Drug MM-121 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment
A Phase 1 study testing MM-121 in people with Advanced Solid Tumors, run by Merrimack Pharmaceuticals at 3 sites in United States.
Trial summary
This study was a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design to determine maximum tolerated dose/recommended Phase 2 dose. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- MM-121
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2008to Sep 2013
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed advanced solid tumors that have recurred or progressed following standard therapy, or that have not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
- Patients must be > 18 years of age
- Patients or their legal representatives must be able to understand and sign an informed consent form
- Patients must have evaluable or measurable tumor(s)
- Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for patients with known peripheral neuropathy.
- Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-121 (an effective form of contraception is an oral contraceptive or a double barrier method)
Show all 15Show fewer
- In addition, patients to be enrolled the Expansion Cohort must have/be:
- Advanced/metastatic breast cancer with histological/cytological documentation of ER-, PR-, Her2/neu non-over-expressing breast cancer (triple negative breast cancer); OR,
- Patients must have advanced/metastatic breast cancer with histologically or cytologically confirmed ER+ and/or PR+, Her2/neu non-over-expxressing OR,
- Patients must have advanced/metastatic histological confirmation of epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer; OR,
- Additional tumor types such as metastatic colorectal, advanced non small cell lung cancer, and others may be considered on a per-patient basis
- Tumor tissue amenable to biopsy
- Platelet counts, partial thromboplastin time (PTT) and international normalized ratio (INR) within normal limits.
- Willing to undergo tumor biopsy twice (once before and once after treatment with MM-121)
- Blocks of archived formalin-fixed, paraffin-embedded, unstained tumor tissue available for submission. Patients with no available archived tumor tissue available must receive Sponsor approval prior to enrollment.
Who cannot join
- Patients for whom potentially curative antineoplastic therapy is available
- Patients who are pregnant or lactating
- Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, patients with tumor fever may be enrolled.)
- Patients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial
- NYHA Class III or IV congestive heart failure or LVEF < 55%
- Known HIV, hepatitis B or C (active, previously treated or both)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115-6084
The Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
Official title: A Phase I and Pharmocologic Study of MM-121 in Patients With Refractory Advanced Solid Tumors
This study was a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design to determine maximum tolerated dose/recommended Phase 2 dose.
Read the detailed description
Successive cohorts of three or more patients were treated at escalating doses until a maximum tolerated dose/recommended phase 2 dose was identified. The study initially explored a dosing schedule every 7-days, which may have been modified to longer intervals under certain circumstances but did not expand to more than weekly. When the maximum tolerated dose/recommended Phase 2 dose was identified, an Expansion Cohort was enrolled at that dose to further characterize safety and to explore pharmacodynamic endpoints. There were 3 sites that participated.
- Conditions
- Advanced Solid Tumors
- Being tested
- MM-121
- Keywords
- cancer, solid tumors, oncology, Phase I, ErbB3, HER3, (erbB-3, HER-3)
- Medical subject headings
- Neoplasms, Lethal Congenital Contracture Syndrome 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MM-121Drug
Also called Seribantumab, SAR256212
Dose escalation Frequency - once weekly
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Cohorts of escalating doses of MM-121 administered IV QW to determine MTD or RP2D + expansion cohort at MTD/RP2D Receives: Drug: MM-121 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate and Duration
To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response is defined as a >20% decrease in tumor burden from baseline and a Complete Response is defined as complete disappearance of tumor burden from baseline. Duration of response is defined as the length of time in weeks from observation of response until progression.
NOTE: because no patients experienced an objective response as shown below, duration of response is not presented. No duration of response could be measured.
Measured: Time from first dose to date of progression, with a median of 7.1 weeks
Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort from cohort 1-6. Cohort 1 began at 3.2 mg/kg IV QW and the dose escalated in separate cohorts from 6 mg/kg IV QW, 10 mg/kg IV QW, 15 mg/kg IV QW, 20 mg/kg IV QW, to the highest scheduled testing dose at 40 mg/kg one-time loading dose on cycle 1, week 1 followed by 20 mg/kg IV QW maintenance doses. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose and was used to open the expansion cohort.
Measured: From date of first dose to 30 days after termination, the longest 47 weeks
Secondary outcomes (3)
To Describe the Dose-limiting Toxicity of MM-121 as a Monotherapy
To establish the safety of escalating doses of MM-121 administered as a monotherapy in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD to be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.
Measured: From date of first dose to 30 days after termination, the longest 47 weeks
To Determine the Pharmacokinetic and Immunogenicity Parameters of MM-121
Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg).
Immunogenicity data is not available.
Measured: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
To Determine the Pharmacokinetic Parameters of MM-121
Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The AUC is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg).
Measured: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startJul 2008
- Primary completionMay 2010
- Study completionSep 2013
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merrimack Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Crystal Denlinger, MD, Principal investigator, Fox Chase Cancer CenterKwok Kin Wong, MD, Principal investigator, Dana-Farber Cancer InstituteKeedy L Vicki, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734305
- Sponsor's protocol ID
- MM-121-01-100
- Other IDs
- MM-121
- Status last verified
- Aug 2016
- First submitted
- 12 Aug 2008
- Last updated
- 1 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Denlinger CS, Keedy VL, Moyo V, MacBeath G, Shapiro GI. Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Invest New Drugs. 2021 Dec;39(6):1604-1612. doi: 10.1007/s10637-021-01145-y. Epub 2021 Jul 11.
PubMed 34250553
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I and Pharmocologic Study of MM-121 in Patients With Refractory Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00734305
- Acronym / sponsor ID
- MM-121-01-100
- Conditions
- Advanced Solid Tumors
- Keywords
- cancer, solid tumors, oncology, Phase I, ErbB3, HER3, (erbB-3, HER-3)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Merrimack PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Study start
- Jul 2008
- Primary completion
- May 2010 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 14 Aug 2008 (estimated)
- Results
- Posted 1 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design to determine maximum tolerated dose/recommended Phase 2 dose.
Detailed description
Successive cohorts of three or more patients were treated at escalating doses until a maximum tolerated dose/recommended phase 2 dose was identified. The study initially explored a dosing schedule every 7-days, which may have been modified to longer intervals under certain circumstances but did not expand to more than weekly. When the maximum tolerated dose/recommended Phase 2 dose was identified, an Expansion Cohort was enrolled at that dose to further characterize safety and to explore pharmacodynamic endpoints. There were 3 sites that participated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: MM-121Cohorts of escalating doses of MM-121 administered IV QW to determine MTD or RP2D + expansion cohort at MTD/RP2D |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have histologically or cytologically confirmed advanced solid tumors that have recurred or progressed following standard therapy, or that have not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
- Patients must be > 18 years of age
- Patients or their legal representatives must be able to understand and sign an informed consent form
- Patients must have evaluable or measurable tumor(s)
- Advanced/metastatic breast cancer with histological/cytological documentation of ER-, PR-, Her2/neu non-over-expressing breast cancer (triple negative breast cancer); OR,
Key exclusion criteria (6 listed)
- Patients for whom potentially curative antineoplastic therapy is available
- Patients who are pregnant or lactating
- Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, patients with tumor fever may be enrolled.)
- Patients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial
- NYHA Class III or IV congestive heart failure or LVEF < 55%
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 |
|---|---|---|
| MM-121Also: Seribantumab, SAR256212Dose escalation Frequency - once weekly | Drug | Dose Escalation |
Primary outcome
Objective Response Rate and Duration
Time frame: Time from first dose to date of progression, with a median of 7.1 weeks
To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response is defined as a >20% decrease in tumor burden from baseline and a Complete Response is defined as complete disappearance of tumor burden from baseline. Duration of response is defined as the length of time in weeks from observation of response until progression. NOTE: because no patients experienced an objective response as shown below, duration of response is not presented. No duration of response could be measured.
Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
Time frame: From date of first dose to 30 days after termination, the longest 47 weeks
Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort from cohort 1-6. Cohort 1 began at 3.2 mg/kg IV QW and the dose escalated in separate cohorts from 6 mg/kg IV QW, 10 mg/kg IV QW, 15 mg/kg IV QW, 20 mg/kg IV QW, to the highest scheduled testing dose at 40 mg/kg one-time loading dose on cycle 1, week 1 followed by 20 mg/kg IV QW maintenance doses. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose and was used to open the expansion cohort.
3 secondary outcomes
To Describe the Dose-limiting Toxicity of MM-121 as a Monotherapy
Time frame: From date of first dose to 30 days after termination, the longest 47 weeks
To Determine the Pharmacokinetic and Immunogenicity Parameters of MM-121
Time frame: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
To Determine the Pharmacokinetic Parameters of MM-121
Time frame: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34250553Denlinger CS, Keedy VL, Moyo V, MacBeath G, Shapiro GI. Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Invest New Drugs. 2021 Dec;39(6):1604-1612. doi: 10.1007/s10637-021-01145-y. Epub 2021 Jul 11.
- Individual participant dataSharing planned: No
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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.
Crystal Denlinger, MD principal investigator
Fox Chase Cancer Center
Kwok Kin Wong, MD principal investigator
Dana-Farber Cancer Institute
Keedy L Vicki, MD principal investigator
Vanderbilt University Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MM-121 in people with Advanced Solid Tumors, run by Merrimack Pharmaceuticals at 3 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 6 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 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 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.
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 1 Sep 2016). 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 and Duration (time frame: Time from first dose to date of progression, with a median of 7.1 weeks). 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?
On the ClinicalTrials.gov record for NCT00734305, 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 1 Sep 2016.