Non Small Cell Lung Cancer MetastaticPhase 2NCT05117242
Safety and Efficacy Study of GEN1046 as a Single Agent or in Combination With Pembrolizumab for Treatment of Recurrent (Non-small Cell) Lung Cancer
A Phase 2 study testing Acasunlimab and Pembrolizumab in people with Non Small Cell Lung Cancer Metastatic, run by Genmab at 40 sites in 9 countries.
Trial summary
The goal of this clinical trial is to compare the safety and efficacy (how well the drug works) of acasunlimab (also known as GEN1046) when it is used alone (monotherapy) versus when it is combined with a cancer drug (pembrolizumab) for participants with relapsed/refractory (disease has returned after treatment or did… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer Metastatic
- What is being tested?
- Acasunlimab and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 40 sitesin 9 countries
- Study dates
- 27 Oct 2021to 31 Aug 2026
- Phase
- Phase 2
- 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
- Have signed an informed consent form (ICF)
- Be at least 18 years of age.
- Have histologically or cytologically confirmed diagnosis of stage 4 NSCLC with at least 1 prior line of systemic therapy containing an anti-PD-1/PD-L1 mAb for metastatic disease
- Have a tumor PD-L1 expression result available prior to first treatment demonstrating PD-L1 expression in ≥1% of tumor cells as assessed by a central or local laboratory during screening.
- Have measurable disease per RECIST v1.1.
- Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
- Have life expectancy of at least 3 months.
- Have adequate organ and bone marrow function as defined in the protocol.
Who cannot join
- Documentation of known EGFR, KRAS, RET, ROS1, BRAF mutations, NTRK gene infusions, RET arrangement, ALK gene rearrangements, high-level MET amplification, or METex 14 skipping. Note: Subjects harboring such mutations, gene rearrangements or amplifications may be enrolled in the trial, if subjects have received prior approved targeted therapy for such mutations, the subject may still be eligible for this trial.
- Treatment with an anti-cancer agent within 28 days prior to acasunlimab administration.
- Any investigational agent (including investigational vaccines).
- Radiotherapy within 14 days prior to first dose of acasunlimab. Note: palliative radiotherapy will be allowed for local pain control under certain conditions.
- Chronic systemic immunosuppressive corticosteroid doses, ie, prednisone >10 mg daily or a cumulative dose >150 mg prednisone within 14 days before the first acasunlimab administration.
- Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
Show all 19Show fewer
- Subject has contraindications to the use of pembrolizumab per local prescribing information.
- Subject has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis (interstitial lung disease).
- Ongoing or active infection requiring intravenous treatment with anti-infective therapy or any ongoing systemic inflammatory condition requiring further diagnostic work-up or management during screening.
- Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia.
- Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management.
- Ongoing or recent (within 6 months) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs.
- Subject has a known history of any of the following:
- Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment.
- Myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
- Liver disease (eg, alcoholic hepatitis or non-alcoholic steatohepatitis, drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis).
- Organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of acasunlimab.
- Grade 3 or higher allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial.
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
40 sites in 9 countries.
40 sites in 9 countries
Spain8 sites
Hospital Universitari Vall dHebron
Barcelona
Clinica Universidad de Navarra CUN
Madrid
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario Fundacion Jimenez Diaz
Madrid
MD Anderson Cancer Center
Madrid
Hospital Universitario Virgen de la Victoria
Málaga
Clinica Universidad de Navarra
Pamplona
Fundacion Instituto Valenciano de Oncologia
Valencia
France7 sites
Institut Bergonie
Bordeaux
Hopital Morvan CHU de Brest
Brest
Hopital Charles Nicolle Chu Rouen
Rouen
Hopital dInstruction Des Armees Begin
Saint-Mandé
Institut de Cancerologie Strasbourg Europe (ICANS)
Strasbourg
Hôpital Foch
Suresnes
Gustave Roussy
Villejuif
United States6 sites
Henry Ford Cancer Institute
Detroit, Michigan, 48202
Florida Cancer Specialists - FCS South
Fort Myers, Florida, 33901
Cancer & Hematology Centers of Western Michigan CHCWM P.C.
Grand Rapids, Michigan, 49503
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
St. Joseph Heritage Healthcare
Santa Rosa, California, 95403
Florida Cancer Center
St. Petersburg, Florida, 33705
Italy5 sites
Azienda Ospedaliera Universitaria Policlinico G Rodolico San Marco
Catania
IRCCS Istituto Europeo di Oncologia
Milan
UOC Oncoematologia AOU L.Vanvitelli
Naples
La Maddalena SPA
Palermo
IFO Regina Elena
Roma
Germany4 sites
Med.Hochschule Hannover Klinik für Pneumologie
Hanover
Universitatsklinik Giessen und Marburg Standort Giessen
Hessen
LKI Lungenfachklinik Immenhausen
Immenhausen
Department of Internal Medicine II
Regensburg
Netherlands4 sites
Netherlands Cancer Institute
Amsterdam
VU University Medical Center
Amsterdam
Leids Universitair Medisch Centrum
Leiden
Erasmus MC
Rotterdam
Poland2 sites
Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
Olsztyn
Maria Sklodowska-Curie National Research Institute of Oncology
Warsaw
Portugal2 sites
Centro Clinico Champalimaud
Lisbon
Centro Hospitalar Universitário do Porto - Hospital de Santo Antonio
Porto
United Kingdom2 sites
Cheltenham General Hospital
Cheltenham
The Christie Hospital
Manchester
About this study
Official title: A Phase 2, Multicenter, Randomized, Open-Label Trial of GEN1046 as Monotherapy and in Combination Pembrolizumab Therapy in Subjects With Relapsed/Refractory Metastatic Non-Small Cell Lung Cancer After Treatment With Standard of Care Therapy With an Immune Checkpoint Inhibitor
The goal of this clinical trial is to compare the safety and efficacy (how well the drug works) of acasunlimab (also known as GEN1046) when it is used alone (monotherapy) versus when it is combined with a cancer drug (pembrolizumab) for participants with relapsed/refractory (disease has returned after treatment or did not respond to treatment) non-small cell lung cancer (NSCLC; the most common type of lung cancer).
This trial has 2 parts. The purpose of the first part is to find out if the combination of acasunlimab and pembrolizumab is safe and to find out the best doses to use. The purpose of the second part is to give acasunlimab and pembrolizumab to more participants to evaluate efficacy. In the second part of the trial, participants will be randomized to participate in 1 of the 3 arms of the trial. Randomized means that the participant will be randomly assigned to a treatment arm based on chance; no one chooses their treatment arm.
Read more
Participants will receive either acasunlimab alone (100 followed by 500 mg into the vein) or acasunlimab with pembrolizumab (200 or 400 mg into the vein) once every 3 or 6 weeks, depending on which arm the participant is randomized into. All participants will receive active drug; no one will receive placebo.
Trial details include:
- The average trial duration for an individual participant will be about 10 months.
- The average treatment duration for an individual participant will be about 6 months.
- The visit frequency will be weekly at first and lessening over time until visits are only once every 3 weeks.
- Conditions
- Non Small Cell Lung Cancer Metastatic
- Being tested
- Acasunlimab, Pembrolizumab
- Keywords
- DuoBody®, Bispecific antibody, PD-L1, 4-1BB
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcasunlimabBiological
Also called GEN1046, DuoBody®-PD-L1×4-1BB
Acasunlimab will be administered intravenously (IV)
PembrolizumabBiological
Also called KEYTRUDA®
Pembrolizumab will be administered IV
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Treatment with acasunlimab once every 21 days for the first 2 cycles and then every 42 days in subsequent cycles Receives: Biological: Acasunlimab |
| Arm B | Experimental | Treatment with acasunlimab + pembrolizumab once every 21 days Receives: Biological: Acasunlimab; Biological: Pembrolizumab |
| Arm C | Experimental | Treatment with acasunlimab + pembrolizumab once every 42 days Receives: Biological: Acasunlimab; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
ORR will be measured as the proportion of subjects with a confirmed response of complete response (CR) or partial response (PR) as per RECIST v1.1
Measured: From first treatment to approximately 27 weeks after last subject's first dose
Secondary outcomes (5)
Duration of response (DOR)
DOR will be measured as the time from initial onset of CR or PR to first radiographic progression as per RECIST v. 1.1 or death from any cause, whichever occurs first.
Measured: From onset date of response until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
Time to response (TTR)
TTR will be measured as the time from first treatment to onset of initial response (CR or PR) as per RECIST v.1.1
Measured: From first treatment to date of onset of initial response (CR or PR) as per RECIST v.1.1 (an expected average of 6 months)
Progression-free survival (PFS)
PFS will be measured from date of first treatment until date of radiographic progression as per RECIST v.1.1 or until death from any cause, whichever occurs first
Measured: From first treatment to first documented progression or death due to any cause (an expected average of 6 months)
Overall survival (OS)
Defined as time to death from of any cause
Measured: From first treatment to date of death (assessed up to 3 years after the last participant's first dose in the trial)
Incidence and severity of adverse events (AEs) and laboratory abnormalities
Incidence of treatment-emergent AEs as assessed by CTCAE v5.0. Laboratory parameters graded by CTCAE v5.0
Measured: Throughout the trial until end of safety follow-up period (60 days or 90 days after last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2021
- Study start27 Oct 2021
- Primary completion2 Dec 2024
- Study completion31 Aug 2026
Why it stopped: Genmab has decided to discontinue further clinical development of acasunlimab following strategic portfolio prioritization. The decision was not related to safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by GenmabThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genmab
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Study Official, Study director, Genmab
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05117242
- Sponsor's protocol ID
- GCT1046-04
- Other IDs
- 2021-001928-17, 1004314, NL-OMON54259, 2024-513770-22-00, RECF-005102, 15582
- Status last verified
- Sep 2026
- First submitted
- 1 Nov 2021
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Randomized, Open-Label Trial of GEN1046 as Monotherapy and in Combination Pembrolizumab Therapy in Subjects With Relapsed/Refractory Metastatic Non-Small Cell Lung Cancer After Treatment With Standard of Care Therapy With an Immune Checkpoint Inhibitor
- ClinicalTrials.gov ID
- NCT05117242
- Acronym / sponsor ID
- GCT1046-04
- Conditions
- Non Small Cell Lung Cancer Metastatic
- Keywords
- DuoBody®, Bispecific antibody, PD-L1, 4-1BB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Genmab has decided to discontinue further clinical development of acasunlimab following strategic portfolio prioritization. The decision was not related to safety concerns.
- Enrolment
- 125 participants (actual)
- Lead sponsor
- GenmabIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 27 Oct 2021 (actual)
- Primary completion
- 2 Dec 2024 (actual)
- Study completion
- 31 Aug 2026 (actual)
- First posted
- 11 Nov 2021 (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.
The goal of this clinical trial is to compare the safety and efficacy (how well the drug works) of acasunlimab (also known as GEN1046) when it is used alone (monotherapy) versus when it is combined with a cancer drug (pembrolizumab) for participants with relapsed/refractory (disease has returned after treatment or did not respond to treatment) non-small cell lung cancer (NSCLC; the most common type of lung cancer).
This trial has 2 parts. The purpose of the first part is to find out if the combination of acasunlimab and pembrolizumab is safe and to find out the best doses to use. The purpose of the second part is to give acasunlimab and pembrolizumab to more participants to evaluate efficacy. In the second part of the trial, participants will be randomized to participate in 1 of the 3 arms of the trial. Randomized means that the participant will be randomly assigned to a treatment arm based on chance; no one chooses their treatment arm.
Participants will receive either acasunlimab alone (100 followed by 500 mg into the vein) or acasunlimab with pembrolizumab (200 or 400 mg into the vein) once every 3 or 6 weeks, depending on which arm the participant is randomized into. All participants will receive active drug; no one will receive placebo.
Trial details include:
- The average trial duration for an individual participant will be about 10 months.
- The average treatment duration for an individual participant will be about 6 months.
- The visit frequency will be weekly at first and lessening over time until visits are only once every 3 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Biological: AcasunlimabTreatment with acasunlimab once every 21 days for the first 2 cycles and then every 42 days in subsequent cycles |
| Arm B | Experimental | Biological: Acasunlimab, Biological: PembrolizumabTreatment with acasunlimab + pembrolizumab once every 21 days |
| Arm C | Experimental | Biological: Acasunlimab, Biological: PembrolizumabTreatment with acasunlimab + pembrolizumab once every 42 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Have signed an informed consent form (ICF)
- Be at least 18 years of age.
- Have histologically or cytologically confirmed diagnosis of stage 4 NSCLC with at least 1 prior line of systemic therapy containing an anti-PD-1/PD-L1 mAb for metastatic disease
- Have a tumor PD-L1 expression result available prior to first treatment demonstrating PD-L1 expression in ≥1% of tumor cells as assessed by a central or local laboratory during screening.
- Have measurable disease per RECIST v1.1.
Key exclusion criteria (19 listed)
- Documentation of known EGFR, KRAS, RET, ROS1, BRAF mutations, NTRK gene infusions, RET arrangement, ALK gene rearrangements, high-level MET amplification, or METex 14 skipping. Note: Subjects harboring such mutations, gene rearrangements or amplifications may be enrolled in the trial, if subjects have received prior approved targeted therapy for such mutations, the subject may still be eligible for this trial.
- Treatment with an anti-cancer agent within 28 days prior to acasunlimab administration.
- Any investigational agent (including investigational vaccines).
- Radiotherapy within 14 days prior to first dose of acasunlimab. Note: palliative radiotherapy will be allowed for local pain control under certain conditions.
- Chronic systemic immunosuppressive corticosteroid doses, ie, prednisone >10 mg daily or a cumulative dose >150 mg prednisone within 14 days before the first acasunlimab administration.
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 |
|---|---|---|
| AcasunlimabAlso: GEN1046, DuoBody®-PD-L1×4-1BBAcasunlimab will be administered intravenously (IV) | Biological | Arm A, Arm B, Arm C |
| PembrolizumabAlso: KEYTRUDA®Pembrolizumab will be administered IV | Biological | Arm B, Arm C |
Primary outcome
Objective response rate (ORR)
Time frame: From first treatment to approximately 27 weeks after last subject's first dose
ORR will be measured as the proportion of subjects with a confirmed response of complete response (CR) or partial response (PR) as per RECIST v1.1
5 secondary outcomes
Duration of response (DOR)
Time frame: From onset date of response until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
Time to response (TTR)
Time frame: From first treatment to date of onset of initial response (CR or PR) as per RECIST v.1.1 (an expected average of 6 months)
Progression-free survival (PFS)
Time frame: From first treatment to first documented progression or death due to any cause (an expected average of 6 months)
Overall survival (OS)
Time frame: From first treatment to date of death (assessed up to 3 years after the last participant's first dose in the trial)
Incidence and severity of adverse events (AEs) and laboratory abnormalities
Time frame: Throughout the trial until end of safety follow-up period (60 days or 90 days after last dose)
Results and safety
The study was stopped early (reason given: Genmab has decided to discontinue further clinical development of acasunlimab following strategic portfolio prioritization. The decision was not related to safety concerns.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- 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.
Study Official study director
Genmab
40 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acasunlimab and Pembrolizumab in people with Non Small Cell Lung Cancer Metastatic, run by Genmab at 40 sites in 9 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 8 inclusion and 19 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 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in Spain, France, United States, Italy, Germany and 4 more countries. 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?
The study was stopped early (reason given: Genmab has decided to discontinue further clinical development of acasunlimab following strategic portfolio prioritization. The decision was not related to safety concerns.). Results are not available in the source record.
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 (ORR) (time frame: From first treatment to approximately 27 weeks after last subject's first dose). 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 21 Sep 2026.