Safety and Efficacy Study of GEN1046 as a Single Agent or in Combination With Pembrolizumab for Treatment of Recurrent (Non-small Cell) Lung Cancer

• ClinicalTrials.gov Identifier: NCT05117242
• Recruitment Status: Recruiting
• First Posted: November 11, 2021
• Last Update Posted: April 3, 2024
• Sponsor: Genmab
• Collaborators: BioNTech SE; Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Genmab

Tracking Information

• First Submitted Date: November 1, 2021
• First Posted Date: November 11, 2021
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: October 27, 2021
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2024)

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

Original Primary Outcome Measures (submitted: November 10, 2021)

Objective response rate (ORR) [ Time Frame: The objective response rate will be assessed from first treatment until 6 months after last subjects first treatment ]

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

Current Secondary Outcome Measures (submitted: August 25, 2022)

• 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) ]
  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.
• 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) ]
  TTR will be measured as the time from first treatment to onset of initial response (CR or PR) as per RECIST v.1.1
• 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) ]
  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
• 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) ]
  Defined as time to death from of any cause
• 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) ]
  Incidence of treatment-emergent AEs as assessed by CTCAE v5.0. Laboratory parameters graded by CTCAE v5.0

Original Secondary Outcome Measures (submitted: November 10, 2021)

• Duration of response [ Time Frame: Duration of response will be assessed from first treatment until 6 months after last subjects first treatment ]
  Duration of response will be measured as the time from initial onset of confirmed response (CR or PR) to first radiographic progression as per RECIST v. 1.1 or death from any cause, whichever occurs first.
• Time to response [ Time Frame: Time to response will be assessed from first treatment until 6 months after last subjects first treatment ]
  Time to response will be measured as the time from first treatment to onset of initial response (CR or PR) as per RECIST v.1.1
• Progression-free survival [ Time Frame: Progression-free survival will be assessed from first treatment until 6 months after last subjects first treatment ]
  Progression-free survival 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
• Overall survival [ Time Frame: Overall survival will be assessed from first treatment until 6 months after last subjects first treatment ]
  Overall survival will be measured from date of first treatment until death from any cause
• Incidence and severity of adverse events and laboratory abnormalities [ Time Frame: Adverse events and safety laboratory data are collected from first treatment until 6 months after last subjects first treatment ]
  Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0. Laboratory parameters graded by CTCAE v5.0

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy Study of GEN1046 as a Single Agent or in Combination With Pembrolizumab for Treatment of Recurrent (Non-small Cell) Lung Cancer
• 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
• Brief Summary: The purpose of this trial is to investigate the safety and efficacy of acasunlimab (also known as GEN1046) as monotherapy and in combination with pembrolizumab in patients with non-small cell lung cancer who have progressed during or after treatment of previous standard of care

Detailed Description

This trial is a randomized, open-label trial evaluating the safety and efficacy of acasunlimab (GEN1046) as monotherapy and in combination therapy with pembrolizumab.

The trial consists of two parts; a safety phase and an extension phase. The extension phase will be initiated once the safety phase is completed.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer Metastatic

Intervention

• Biological: Acasunlimab
  Acasunlimab will be administered intravenously (IV)
  Other Names:

  • GEN1046
  • DuoBody®-PD-L1×4-1BB
• Biological: Pembrolizumab
  Pembrolizumab will be administered IV
  Other Name: KEYTRUDA®

Study Arms

• Experimental: Arm A
  Treatment with acasunlimab once every 21 days for the first 2 cycles and then every 42 days in subsequent cycles
  Intervention: Biological: Acasunlimab
• Experimental: Arm B
  Treatment with acasunlimab + pembrolizumab once every 21 days
  Interventions:

  • Biological: Acasunlimab
  • Biological: Pembrolizumab
• Experimental: Arm C
  Treatment with acasunlimab+ pembrolizumab once every 42 days
  Interventions:

  • Biological: Acasunlimab
  • Biological: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 25, 2022): 160
• Original Estimated Enrollment (submitted: November 10, 2021): 126
• Estimated Study Completion Date: March 2027
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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 for the treatment of stage 4 NSCLC.
• 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.
• 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:

  1. Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment.
  2. Myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
  3. Liver disease (eg, alcoholic hepatitis or non-alcoholic steatohepatitis, drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis).
  4. 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.
  5. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Genmab A/S Trial Information; +45 70202728; clinicaltrials@genmab.com

• Listed Location Countries: France, Germany, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05117242
• Other Study ID Numbers: GCT1046-04; 2021-001928-17 ( EudraCT Number ); 1004314 ( Other Identifier: IRAS ID; UK Research Summaries Database )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Genmab
• Original Responsible Party: Same as current
• Current Study Sponsor: Genmab
• Original Study Sponsor: Same as current

Collaborators

• BioNTech SE
• Merck Sharp & Dohme LLC

• Investigators: Not Provided
• PRS Account: Genmab
• Verification Date: April 2024