Advanced Solid TumorPhase 1/2NCT04442126
A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors
A Phase 1/2 study testing NM21-1480 in people with Advanced Solid Tumor and Non-small Cell Lung Cancer, run by Numab Therapeutics AG at 26 sites in 3 countries.
Trial summary
This is a first-in-human, open-label, multi-center, Phase 1/2, dose-escalation study with expansion cohorts to evaluate NM21-1480 for safety and immunogenicity, to determine the maximal tolerated dose and recommended Phase 2 dose, define the pharmacokinetics, to explore the pharmacodynamics, and to obtain preliminary… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Non-small Cell Lung Cancer, Colorectal Cancer
- What is being tested?
- NM21-1480
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 26 sitesin 3 countries
- Study dates
- 19 Aug 2020to 6 Feb 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Part A
- Patients with any previously treated solid tumor-type other than hepatocellular carcinoma or intrahepatic cholangiocarcinoma that is advanced, or recurrent and progressing since last anti-tumor therapy, and for which no alternative, standard therapy exists.
- Prior chemotherapy, radiation therapy or immunotherapy must have been completed at least 4 weeks prior to the administration of the first dose of study drug, and patient has recovered
- Part B:
- Patients with Non-small Cell Lung Cancer (NSCLC) or other protocol specified solid tumors with locally advanced or metastatic, non-resectable disease, which has progressed despite treatment with first-line standard of-care treatment, or first- and second-line treatment, dependent on expansion cohort.
- Prior therapy must have been completed 2-4 weeks prior to the administration of the first dose of study drug as specified per protocol according to type of prior therapy
Who cannot join
- Patient previously had known immediate or delayed hypersensitivity reaction or idiosyncrasy to the excipients
- Part A: Treatment with any PD-1, or Cytotoxic T-Lymphocyte Associated Protein (CTLA)-4 directed antibody, or with any other immunotherapy within 4 weeks prior to initiation of the study drug.
- Part A: Use of other biological investigational drugs (drugs not marketed for any indication), including use of investigational drugs targeting CD137/4-1BB within at least 5 half-lives (or within 8 weeks, whatever is longer) prior to the administration of the first dose of study drug.
- Part B: As defined per protocol for each expansion cohort, has not been treated with specified first/second-line standard-of-care therapies biological drugs (marketed or investigational) for treatment of the current cancer, or has not adequately recovered from AEs that occurred with prior therapy.
- Patient has an active autoimmune disease or a documented history of autoimmune disease.
Trial locations and contacts
26 sites in 3 countries.
26 sites in 3 countries
United States14 sites
Augusta University Medical Center
Augusta, Georgia, 30912
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
Henry Ford Health System
Detroit, Michigan, 48202
Virginia Cancer Specialists
Fairfax, Virginia, 22031
UCHealth Poudre Valley Hospital
Fort Collins, Colorado, 80524
The University Of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Dartmouth Cancer Center
Lebanon, New Hampshire, 03766
Sarah Cannon Cancer Center
Nashville, Tennessee, 37203
Tulane University Medical Center
New Orleans, Louisiana, 70112
NYU Langone Medical Center - Perlmutter Cancer Center (NYU Cancer Institute)
New York, New York, 10016
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Montefiore Medical Center
The Bronx, New York, 10461-2374
St. Joseph Mercy Hospital
Ypsilanti, Michigan, 48197
Spain11 sites
Hospital Universitario de A Coruna
A Coruña
Hospital Universitario Vall dHebron
Barcelona
Hospital General Universitario de Elche
Elche
Complejo Hospitalario de Jaen
Jaén
Centro Integral Oncologico Clara Campal
Madrid
Clinica Universidad de Navarra - Madrid
Madrid
Hospital Universitario Virgen de la Victoria
Málaga
Hospital Universitario Son Llatzer
Palma de Mallorca
Clinica Universidad de Navarra - Pamplona
Pamplona
Hospital Universitario Virgen Macarena
Seville
Hospital Universitari i Politecnic La Fe
Valencia
About this study
Official title: A Phase 1/2 Study of NM21-1480 (Anti-PDL-1/Anti-4-1BB/Anti-HSA Tri-Specific Antibody) in Adult Patients With Advanced Solid Tumors
This is a first-in-human, open-label, multi-center, Phase 1/2, dose-escalation study with expansion cohorts to evaluate NM21-1480 for safety and immunogenicity, to determine the maximal tolerated dose and recommended Phase 2 dose, define the pharmacokinetics, to explore the pharmacodynamics, and to obtain preliminary evidence of the clinical activity in adult patients with selected advanced solid tumors.
- Conditions
- Advanced Solid Tumor, Non-small Cell Lung Cancer, Colorectal Cancer, Squamous Cell Carcinoma, Ovarian Carcinoma, Peritoneal Carcinoma
- Being tested
- NM21-1480
- Keywords
- Carcinoma, Neoplasms
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Carcinoma, Squamous Cell, Ovarian Neoplasms, Fallopian Tube Neoplasms, Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Neoplasms, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NM21-1480Biological
Trispecific anti-PD-L1/anti-4-1BB/anti-Human Serum Albumin (HSA) single-chain Fv fusion protein
| Study group | Role | What they receive |
|---|---|---|
| NM21-1480 Treatment arm | Experimental | Not described Receives: Biological: NM21-1480 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
Frequency and severity of adverse events
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Maximum Tolerated Dose (MTD) of NM21-1480
To determine the MTD of NM21-1480 based on Part A. Note, No MTD was identified across all dose levels tested and a technical MTD was defined by the SMC as 800 mg following Part A, which was updated to 1400 mg by the SMC after completion of Part A-2.
Measured: Cycle 1 (28 days).
Determination of Phase 2 Dose of NM21-1480
To determine the recommended Phase 2 dose of NM21-1480 for Part B of the study
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
To Determine the Anti-tumor Activity (Best Overall Response) of NM21-1480 According to RECIST 1.1
For best overall response (BOR) and objective response rate (ORR), patients in the Efficacy Analysis Set (EAS) who did not have sufficient on-study tumor assessments to characterize response were included in the denominator when calculating BOR percent and ORR and were thus treated as non-responders.
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Secondary outcomes (13)
Assessment of the Maximum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmax)
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the the Minimum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmin)
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Time From Dosing at Which Cmax is Apparent Determined by Direct Inspection of the Concentration Versus Time Data (Tmax)
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Terminal Phase (Apparent Elimination) Rate Constant (λz)
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Elimination Half-life (t½)
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Area Under the Serum Concentration-time Curve Extrapolated From the Last Quantifiable Concentration to Infinity Quantifiable Concentration to Infinity (AUC[0-infinity])
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Area Under Serum Concentration-time Curve Over Dosing Interval (AUCtau)
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Clearance (CL)
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Volume of Distribution (Vd)
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Frequency of Specific Anti-drug Antibodies to NM21-1480
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
To Determine the Anti-tumor Activity (Duration of Response) of NM21-1480 According to RECIST 1.1
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
To Determine the Anti-tumor Activity (Time-to-response) of NM21-1480 According to RECIST 1.1
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
To Determine the Anti-tumor Activity (Progression-free Survival) of NM21-1480 According to RECIST 1.1
Measured: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2020
- Study start19 Aug 2020
- Primary completion6 Feb 2024
- Study completion6 Feb 2024
Why it stopped: A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.
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 TumorStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Numab Therapeutics AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04442126
- Sponsor's protocol ID
- NB-ND021 (NM21-1480)-101
- Other IDs
- 2020-0355
- Status last verified
- May 2025
- First submitted
- 18 Jun 2020
- Last updated
- 23 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Johansson MU, Kerschenmeyer A, Carella A, Carnal S, Schmidt Y, de Felice A, Mahler D, Thomas M, Spiga FM, Tietz J, Weinert C, Hess C, Urech D, Warmuth S. Structure-guided design of antibody CDRs to reduce their reactivity to treatment-emergent anti-drug antibodies. MAbs. 2026 Dec;18(1):2604353. doi: 10.1080/19420862.2025.2604353. Epub 2025 Dec 22.
PubMed 41424175
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of NM21-1480 (Anti-PDL-1/Anti-4-1BB/Anti-HSA Tri-Specific Antibody) in Adult Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04442126
- Acronym / sponsor ID
- NB-ND021 (NM21-1480)-101
- Conditions
- Advanced Solid Tumor, Non-small Cell Lung Cancer, Colorectal Cancer, Squamous Cell Carcinoma, Ovarian Carcinoma, Peritoneal Carcinoma
- Keywords
- Carcinoma, Neoplasms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Numab Therapeutics AGIndustry (pharma, biotech, devices)
- Study start
- 19 Aug 2020 (actual)
- Primary completion
- 6 Feb 2024 (actual)
- Study completion
- 6 Feb 2024 (actual)
- First posted
- 22 Jun 2020 (actual)
- Results
- Posted 23 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a first-in-human, open-label, multi-center, Phase 1/2, dose-escalation study with expansion cohorts to evaluate NM21-1480 for safety and immunogenicity, to determine the maximal tolerated dose and recommended Phase 2 dose, define the pharmacokinetics, to explore the pharmacodynamics, and to obtain preliminary evidence of the clinical activity in adult patients with selected advanced solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NM21-1480 Treatment arm | Experimental | Biological: NM21-1480 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Part A
- Patients with any previously treated solid tumor-type other than hepatocellular carcinoma or intrahepatic cholangiocarcinoma that is advanced, or recurrent and progressing since last anti-tumor therapy, and for which no alternative, standard therapy exists.
- Prior chemotherapy, radiation therapy or immunotherapy must have been completed at least 4 weeks prior to the administration of the first dose of study drug, and patient has recovered
- Patients with Non-small Cell Lung Cancer (NSCLC) or other protocol specified solid tumors with locally advanced or metastatic, non-resectable disease, which has progressed despite treatment with first-line standard of-care treatment, or first- and second-line treatment, dependent on expansion cohort.
- Prior therapy must have been completed 2-4 weeks prior to the administration of the first dose of study drug as specified per protocol according to type of prior therapy
Key exclusion criteria (5 listed)
- Patient previously had known immediate or delayed hypersensitivity reaction or idiosyncrasy to the excipients
- Part A: Treatment with any PD-1, or Cytotoxic T-Lymphocyte Associated Protein (CTLA)-4 directed antibody, or with any other immunotherapy within 4 weeks prior to initiation of the study drug.
- Part A: Use of other biological investigational drugs (drugs not marketed for any indication), including use of investigational drugs targeting CD137/4-1BB within at least 5 half-lives (or within 8 weeks, whatever is longer) prior to the administration of the first dose of study drug.
- Part B: As defined per protocol for each expansion cohort, has not been treated with specified first/second-line standard-of-care therapies biological drugs (marketed or investigational) for treatment of the current cancer, or has not adequately recovered from AEs that occurred with prior therapy.
- Patient has an active autoimmune disease or a documented history of autoimmune disease.
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 |
|---|---|---|
| NM21-1480Trispecific anti-PD-L1/anti-4-1BB/anti-Human Serum Albumin (HSA) single-chain Fv fusion protein | Biological | NM21-1480 Treatment arm |
Primary outcome
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Frequency and severity of adverse events
Maximum Tolerated Dose (MTD) of NM21-1480
Time frame: Cycle 1 (28 days).
To determine the MTD of NM21-1480 based on Part A. Note, No MTD was identified across all dose levels tested and a technical MTD was defined by the SMC as 800 mg following Part A, which was updated to 1400 mg by the SMC after completion of Part A-2.
Determination of Phase 2 Dose of NM21-1480
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
To determine the recommended Phase 2 dose of NM21-1480 for Part B of the study
To Determine the Anti-tumor Activity (Best Overall Response) of NM21-1480 According to RECIST 1.1
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
For best overall response (BOR) and objective response rate (ORR), patients in the Efficacy Analysis Set (EAS) who did not have sufficient on-study tumor assessments to characterize response were included in the denominator when calculating BOR percent and ORR and were thus treated as non-responders.
13 secondary outcomes
Assessment of the Maximum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmax)
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the the Minimum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmin)
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Time From Dosing at Which Cmax is Apparent Determined by Direct Inspection of the Concentration Versus Time Data (Tmax)
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Terminal Phase (Apparent Elimination) Rate Constant (λz)
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Elimination Half-life (t½)
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Area Under the Serum Concentration-time Curve Extrapolated From the Last Quantifiable Concentration to Infinity Quantifiable Concentration to Infinity (AUC[0-infinity])
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Area Under Serum Concentration-time Curve Over Dosing Interval (AUCtau)
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Clearance (CL)
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Volume of Distribution (Vd)
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Assessment of the Frequency of Specific Anti-drug Antibodies to NM21-1480
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
To Determine the Anti-tumor Activity (Duration of Response) of NM21-1480 According to RECIST 1.1
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
To Determine the Anti-tumor Activity (Time-to-response) of NM21-1480 According to RECIST 1.1
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
To Determine the Anti-tumor Activity (Progression-free Survival) of NM21-1480 According to RECIST 1.1
Time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41424175Johansson MU, Kerschenmeyer A, Carella A, Carnal S, Schmidt Y, de Felice A, Mahler D, Thomas M, Spiga FM, Tietz J, Weinert C, Hess C, Urech D, Warmuth S. Structure-guided design of antibody CDRs to reduce their reactivity to treatment-emergent anti-drug antibodies. MAbs. 2026 Dec;18(1):2604353. doi: 10.1080/19420862.2025.2604353. Epub 2025 Dec 22.
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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.
The record lists no contact. Use the official record to reach the sponsor.
26 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NM21-1480 in people with Advanced Solid Tumor and Non-small Cell Lung Cancer, run by Numab Therapeutics AG at 26 sites in 3 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 5 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 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Spain, Taiwan. 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 23 May 2025). 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?
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 (time frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.). The study lists 4 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 NCT04442126, 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 23 May 2025.