Advanced CancerPhase 1NCT03922204
A Study of Bispecific Antibody MCLA-145 in Patients With Advanced or Metastatic Malignancies
A Phase 1 study testing MCLA-145 and Pembrolizumab (Keytruda) in people with Advanced Cancer and Solid Tumor, Adult, run by Merus B.V. at 8 sites in 4 countries.
Trial summary
This is an open-label, non-randomized, Phase 1 study to determine the safety, tolerability, and preliminary efficacy of MCLA-145 in adult patients with advanced metastatic solid tumors or B-cell lymphomas. The study will be conducted in 2 parts. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer, Solid Tumor, Adult, B-cell Lymphoma, Adult
- What is being tested?
- MCLA-145 and Pembrolizumab (Keytruda)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 8 May 2019to 7 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histologically or cytologically confirmed advanced or recurrent/metastatic solid tumors or B-cell lymphomas, that are considered non-amenable to surgery or other curative treatments or procedures (if applicable)
- Measureable disease per RECIST v1.1 or Lugano Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Received prior standard therapy for advanced or recurrent/metastatic disease as applicable to tumor type
- Received a maximum of 4 prior systemic treatment regimens (inclusive of chemotherapy, immunotherapy, and targeted therapy regimens) for advanced or recurrent/metastatic disease
- Life expectancy of ≥12 weeks, as per investigator judgement
Who cannot join
- The following B-cell neoplasms: Burkitt lymphoma, lymphoblastic leukemia/lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia
- Prior therapy containing an anti-PD-L1 agent or T-cell agonist
- Current serious illness or medical condition including, but not limited to uncontrolled active infection
- Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting MCLA-145
- Prior ≥ Grade 3 immune-mediated AEs with anti-PD-1 therapy
- History of any grade immune-mediated ocular AEs.
- Known hypersensitivity or severe reaction to any component of MCLA-145 or formulation components
- Participants who have active or inactive autoimmune disease or syndrome (eg, rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that has required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States3 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Moores Cancer Centre
La Jolla, California, 92093-0987
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Belgium2 sites
University Hospital Antwerp
Antwerp, Edegem, 2650
Universitair Ziekenhuis Gent
Ghent, 9000
Spain2 sites
Hospital Universitario Fundarcion Jimenez Diaz
Madrid, 28040 EP
Clinica Universidad de Navarra
Pamplona, 31008 EP
About this study
Official title: A Phase 1, Open-Label, Dose-Escalation, Safety, Tolerability, and Preliminary Efficacy Study of MCLA-145 in Participants With Advanced or Metastatic Malignancies
This is an open-label, non-randomized, Phase 1 study to determine the safety, tolerability, and preliminary efficacy of MCLA-145 in adult patients with advanced metastatic solid tumors or B-cell lymphomas. The study will be conducted in 2 parts.
Read the detailed description
Study Design: This open label, multicenter, first in human study consists of 2 parts. Part 1 is a dose escalation to find the recommended dose of MCLA-145 in monotherapy or in combination with pembrolizumab.
Part 2 is a dose expansion to confirm the dose of MCLA-145, alone or in combination through further evaluation of safety, tolerability, Pk, preliminary antitumor activity, and functional target engagement.
The study includes three periods: Screening (up to 28 days prior to the first dose of study drug); Treatment (first dose of study drug with treatment cycles of 28 days for patients treated Q2W and 21 days for patients treated Q3W); Safety Follow-up (30 and 90 days after the last dose) including survival follow-up checks every 2 months up to 12 months after the last dose.
- Conditions
- Advanced Cancer, Solid Tumor, Adult, B-cell Lymphoma, Adult
- Being tested
- MCLA-145, Pembrolizumab (Keytruda)
- Keywords
- First-in-human, MCLA-145, Antibodies, Bispecific
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MCLA-145Drug
Also called bispecific
full-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137
Pembrolizumab (Keytruda)Drug
Group B patients will be treated in combination with MCLA-145 and pembrolizumab 200mg Q3W.
| Study group | Role | What they receive |
|---|---|---|
| MCLA-145 | Experimental | In Part 1, the dose escalation phase, patients with advanced or recurrent/metastatic solid tumors or B-cell lymphomas will receive escalating doses of MCLA-145 (either Q2W for those patients in treatment at the time of Amendment #4 or Q3W with Amendment #4 approval). Treatment will be with MCLA-145 (monotherapy) for Group A, or in combination with pembrolizumab for Group B, until MTD or RDE is reached. In Part 2, the expansion phase, participants with advanced or metastatic solid tumors will receive intravenous infusion of MCLA-145 either in monotherapy (Group A) or in combination with pembrolizumab (Group B) at the recommended phase II dose every 3 weeks. The duration of each treatment cycle is 21 days Receives: Drug: MCLA-145 |
| Group B Combination Treatment | Experimental | Patients in Group B will be treated with MCLA-145 in Combination with pembrolizumab 200mg Q3W. Receives: Drug: MCLA-145; Drug: Pembrolizumab (Keytruda) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with Dose Limiting Toxicities
Measured: first 28 days of treatment
Number of patients with Adverse Events and Serious Adverse Events
Measured: up to 90 days post-last dose
Secondary outcomes (8)
Overall response rate (ORR)
Measured: Every 8 to 12 weeks until study ends, approximately 4 years
Duration of response ( DOR)
Measured: Every 8 to 12 weeks until study ends, approximately 4 years
Disease control rate ( DCR)
Measured: Every 8 to 12 weeks until study ends, approximately 4 years
Progression Free Survival ( PFS)
Measured: Every 8 to 12 weeks until study ends, approximately 4 years
Incidence of anti-drug antibodies against MCLA-145
Measured: 12 months
Peak plasma concentration [Cmax]
Measured: 12 months
Area under the plasma concentration versus time curve [AUC]
Measured: 12 months
Half-life [t1/2]
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2019
- Study start8 May 2019
- Primary completion7 Nov 2024
- Study completion7 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced CancerStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merus B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gianluca Laus, MD, Study director, Merus B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03922204
- Sponsor's protocol ID
- MCLA-145-CL01/MCLA-145-101
- Other IDs
- 2018-004396-13, 2018
- Status last verified
- Dec 2024
- First submitted
- 15 Apr 2019
- Last updated
- 11 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Dose-Escalation, Safety, Tolerability, and Preliminary Efficacy Study of MCLA-145 in Participants With Advanced or Metastatic Malignancies
- ClinicalTrials.gov ID
- NCT03922204
- Acronym / sponsor ID
- MCLA-145-CL01/MCLA-145-101
- Conditions
- Advanced Cancer, Solid Tumor, Adult, B-cell Lymphoma, Adult
- Keywords
- First-in-human, MCLA-145, Antibodies, Bispecific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Merus B.V.Industry (pharma, biotech, devices)
- Study start
- 8 May 2019 (actual)
- Primary completion
- 7 Nov 2024 (actual)
- Study completion
- 7 Nov 2024 (actual)
- First posted
- 19 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, non-randomized, Phase 1 study to determine the safety, tolerability, and preliminary efficacy of MCLA-145 in adult patients with advanced metastatic solid tumors or B-cell lymphomas. The study will be conducted in 2 parts.
Detailed description
Study Design: This open label, multicenter, first in human study consists of 2 parts. Part 1 is a dose escalation to find the recommended dose of MCLA-145 in monotherapy or in combination with pembrolizumab.
Part 2 is a dose expansion to confirm the dose of MCLA-145, alone or in combination through further evaluation of safety, tolerability, Pk, preliminary antitumor activity, and functional target engagement.
The study includes three periods: Screening (up to 28 days prior to the first dose of study drug); Treatment (first dose of study drug with treatment cycles of 28 days for patients treated Q2W and 21 days for patients treated Q3W); Safety Follow-up (30 and 90 days after the last dose) including survival follow-up checks every 2 months up to 12 months after the last dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MCLA-145 | Experimental | Drug: MCLA-145In Part 1, the dose escalation phase, patients with advanced or recurrent/metastatic solid tumors or B-cell lymphomas will receive escalating doses of MCLA-145 (either Q2W for those patients in treatment at the time of Amendment #4 or Q3W with Amendment #4 approval). Treatment will be with MCLA-145 (monotherapy) for Group A, or in combination with pembrolizumab for Group B, until MTD or RDE is reached. In Part 2, the expansion phase, participants with advanced or metastatic solid tumors will receive intravenous infusion of MCLA-145 either in monotherapy (Group A) or in combination with pembrolizumab (Group B) at the recommended phase II dose every 3 weeks. The duration of each treatment cycle is 21 days |
| Group B Combination Treatment | Experimental | Drug: MCLA-145, Drug: Pembrolizumab (Keytruda)Patients in Group B will be treated with MCLA-145 in Combination with pembrolizumab 200mg Q3W. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically or cytologically confirmed advanced or recurrent/metastatic solid tumors or B-cell lymphomas, that are considered non-amenable to surgery or other curative treatments or procedures (if applicable)
- Measureable disease per RECIST v1.1 or Lugano Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Received prior standard therapy for advanced or recurrent/metastatic disease as applicable to tumor type
- Received a maximum of 4 prior systemic treatment regimens (inclusive of chemotherapy, immunotherapy, and targeted therapy regimens) for advanced or recurrent/metastatic disease
Key exclusion criteria (8 listed)
- The following B-cell neoplasms: Burkitt lymphoma, lymphoblastic leukemia/lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia
- Prior therapy containing an anti-PD-L1 agent or T-cell agonist
- Current serious illness or medical condition including, but not limited to uncontrolled active infection
- Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting MCLA-145
- Prior ≥ Grade 3 immune-mediated AEs with anti-PD-1 therapy
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 |
|---|---|---|
| MCLA-145Also: bispecificfull-length IgG1 bispecific antibody specifically targeting PD-L1 and CD137 | Drug | Group B Combination Treatment, MCLA-145 |
| Pembrolizumab (Keytruda)Group B patients will be treated in combination with MCLA-145 and pembrolizumab 200mg Q3W. | Drug | Group B Combination Treatment |
Primary outcome
Number of patients with Dose Limiting Toxicities
Time frame: first 28 days of treatment
Number of patients with Adverse Events and Serious Adverse Events
Time frame: up to 90 days post-last dose
8 secondary outcomes
Overall response rate (ORR)
Time frame: Every 8 to 12 weeks until study ends, approximately 4 years
Duration of response ( DOR)
Time frame: Every 8 to 12 weeks until study ends, approximately 4 years
Disease control rate ( DCR)
Time frame: Every 8 to 12 weeks until study ends, approximately 4 years
Progression Free Survival ( PFS)
Time frame: Every 8 to 12 weeks until study ends, approximately 4 years
Incidence of anti-drug antibodies against MCLA-145
Time frame: 12 months
Peak plasma concentration [Cmax]
Time frame: 12 months
Area under the plasma concentration versus time curve [AUC]
Time frame: 12 months
Half-life [t1/2]
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2024.
- 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.
Gianluca Laus, MD study director
Merus B.V.
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MCLA-145 and Pembrolizumab (Keytruda) in people with Advanced Cancer and Solid Tumor, Adult, run by Merus B.V. at 8 sites in 4 countries.
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 6 inclusion and 8 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 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Belgium, Spain, Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients with Dose Limiting Toxicities (time frame: first 28 days of treatment). 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 11 Dec 2024.