Human IgG1 hexavalent antibody against TNFRSF4 for Head and neck squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- Able to understand and provide written informed consent.\n- Life expectancy of >3 months.\n- Adequate organ function, based on screening laboratory tests performed within 3 days of randomization, as defined by the following criteria: a.\tHematological (without transfusion or growth factor support) \tAbsolute neutrophil count (ANC) ≥1.5x 109/L (1500/µL). \tPlatelet count ≥100x109/L (100,000/µL). \tHemoglobin ≥90 g/L (9 g/dL) or ≥5.6 mmol/L. b.\tRenal \tCreatinine (Cr) ≤1.5 x upper limit of normal (ULN) OR \tCreatinine clearance (CrCl) ≥30 mL/min estimated per institutional standard for patients with creatinine levels >1.5 x ULN (estimated glomerular filtration rate may be used instead of Cr or CrCl). c.\tHepatic \tAlbumin ≥2.5 g/dL. \tAspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN; for patients with liver metastases, ≤5 x ULN. \tSerum bilirubin ≤1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). d.\tCoagulation \tInternational normalized ratio (INR) (or prothrombin time [PT]) <1.5 x ULN, unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants. \tPTT (or activated PTT [aPTT]) <1.5 x ULN, except for patients receiving anticoagulants.\n- Female patients of childbearing potential must have a negative highly sensitive pregnancy test within 72 hours prior to randomization and must not be breastfeeding.\n- Fertile male patients and female patients of childbearing potential must be willing to completely abstain from heterosexual sex or agree to use acceptable contraception methods from the time of signing informed consent and for the duration of study treatment through 120 days following the last dose. See Appendix C of full protocol for detailed information on fertility, childbearing potential, and acceptable contraception.\n- Ability, in the Investigator’s judgment, and willingness to adhere to the study visit schedule and comply with all study specific procedures.\n- Age ≥18 years at the time of signing informed consent (minimum age requirement per local regulatory requirements).\n- Histological or cytological documentation of HNSCC diagnosed as R/M and considered incurable by local therapies.\n- Primary tumor location of the oral cavity, oropharynx, hypopharynx, or larynx.\n- Consent to provide the most recently collected and representative tumor tissue specimen suitable for biomarker testing.\n- Confirmed PD-L1 CPS ≥20, as assessed centrally using the PD-L1 IHC 22C3 pharmDx assay on the most recent tumor tissue specimen.\n- Confirmed HPV tumor status for oropharyngeal cancer, as assessed centrally by p16 IHC testing on the most recent tumor tissue specimen. •\tOral cavity, hypopharynx, and larynx cancer are not required to undergo HPV testing.\n- Measurable disease per RECIST v1.1 guidelines. •\tTumor lesion(s) previously irradiated or subjected to other locoregional therapy will be considered measurable only if PD is clearly documented at the lesion(s) after completion of therapy.\n- ECOG PS score of 0-1."}

Exclusion criteria

• {"criterion_text":"- Disease amenable for local therapy administered with curative intent.\n- Receiving systemic steroids (>10 mg oral prednisone per day or equivalent) or other immunosuppressive agents within 7 days prior to randomization or has a diagnosis of immunodeficiency.\n- History of toxicity ≥Grade 3 related to prior immunotherapy leading to treatment discontinuation, or toxicity related to any prior treatment that has not resolved to ≤Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and Grade ≤2 peripheral neuropathy or other toxicities not considered a safety risk per Investigator’s judgment).\n- Life expectancy <3 months.\n- Active tumor bleeding.\n- Rapidly progressing disease or with features that may confer a high risk of tumor associated hemorrhage (including, but not limited to, tumors encasing or infiltrating a major vessel such as carotid, jugular, and bronchial artery, and/or other high-risk features such as an arteriovenous fistula), or uncontrolled tumor pain. The Sponsor’s Medical Monitor is available for consultation.\n- Known allergy or hypersensitivity to INBRX-106, pembrolizumab, or any component of their respective formulations. History of severe hypersensitivity to protein-based therapies, in particular CHO-cell derived antibodies or other mAbs.\n- Current or history of immune-related disease (refer to Appendix B) that required systemic treatment in past 2 years, except for replacement therapy (eg, physiological doses of corticosteroids for treatment of endocrinopathies).\n- History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.\n- History of organ allograft transplantations or allogeneic peripheral blood stem cell transplantation/bone marrow transplantations.\n- History of other invasive malignancy within 5 years prior to screening, except for cancers with very low risk of recurrence including, but not limited to, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, papillary thyroid cancer treated with surgery, or Stage I endometrial cancer. The Sponsor’s Medical Monitor is available for consultation.\n- Primary tumor site (any histology) of nasopharynx or salivary glands or occult primary site.\n- Serious infection requiring oral or intravenous (IV) antibiotics, or other clinically significant infection within 14 days prior to randomization. •\tPatients who fully recovered from serious or clinically significant infections at least 14 days prior to randomization are eligible.\n- Known HIV infection, or positive test for active infection with HBV (eg, hepatitis B surface antigen [HBsAg] and/or total hepatitis B core antibody [HBcAb]) or HCV (eg, RNA). •\tPatients cured of HCV infection (undetectable viral load, sustained virologic response for 3 months after completing treatment), or positive for HCV antibody and negative for HCV RNA are eligible. Patients who are HCV carriers and test positive for HCV RNA are not eligible. •\tFor patients who have been successfully treated for viral hepatitis, the possibility of re-activation of the virus or reinfection with viral hepatitis should be considered by the Investigator and the overall potential benefits associated with study treatment for the patient should be deemed to exceed the overall risks.\n- History or current evidence of any condition, therapy, or laboratory abnormality that in the Investigator’s opinion precludes the individual’s safe participation in and completion of the study.\n- Personal or financial relationship with the Sponsor, a contractual relationship with the Investigator or the study site, or in custody or sanctioned by an official or court order.\n- Progressive disease within 6 months of completion of curatively intended treatment for locoregionally advanced HNSCC.\n- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. •\tPatients with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.\n- Prior systemic therapy (eg, prior chemo-, immune-, or biologic therapy) for recurrent or metastatic HNSCC. •\tPrior systemic therapy completed >6 months prior to signing informed consent is allowed if given as part of multimodal treatment for locoregionally advanced disease with curative intent, and no PD/recurrence occurred within 6 months of its completion. Prior systemic immunotherapy for locoregionally advanced disease with curative intent, including but not limited to anti-PD-(L)1 agents, is allowed if PD/recurrence occurred ≥12 months after its completion.\n- Treatment with any investigational systemic therapy within 28 days prior to randomization, or within 5 half-lives of the investigational drug(s), whichever is longer.\n- Radiotherapy or any locoregional anticancer therapy within 14 days prior to randomization.\n- Major surgical procedure or significant traumatic injury within 28 days prior to randomization. Patients must have also fully recovered from any surgery (major or minor) and/or its complications before randomization.\n- Live vaccine administered within 30 days prior to randomization."}

Primary endpoints

• {"endpoint_text":"- ORR, defined as the proportion of patients with a CR or PR on 2 consecutive occasions ≥4 weeks apart, as determined by the Investigator according to RECIST v1.1.","definition_or_measurement_approach":"Objective Response Rate (ORR): proportion of patients with a Complete Response (CR) or Partial Response (PR) on 2 consecutive assessments at least 4 weeks apart, assessed by Investigator per RECIST v1.1."}
• {"endpoint_text":"- PFS, defined as the time from randomization to first occurrence of PD, as determined by the Investigator according to RECIST v1.1, or death from any cause (whichever occurs first).","definition_or_measurement_approach":"Progression-Free Survival (PFS): time from randomization to first documented disease progression per RECIST v1.1 by Investigator or death from any cause."}
• {"endpoint_text":"- OS, defined as the time from randomization to death from any cause.","definition_or_measurement_approach":"Overall Survival (OS): time from randomization until death from any cause."}

Secondary endpoints

• {"endpoint_text":"- DOR, defined as the time from the first occurrence of a documented objective response to PD, as determined by the Investigator according to RECIST v1.1, or death from any cause (whichever occurs first).","definition_or_measurement_approach":"Duration of Response (DOR): time from first documented objective response to progression per RECIST v1.1 or death."}
• {"endpoint_text":"- CBR, defined as the proportion of patients with SD for ≥12 weeks or a CR or PR, as determined by the Investigator according to RECIST v1.1.","definition_or_measurement_approach":"Clinical Benefit Rate (CBR): proportion of patients with stable disease ≥12 weeks or CR or PR per RECIST v1.1 assessed by Investigator."}
• {"endpoint_text":"- PFS rate at 6 months, defined as the proportion of patients who are progression-free and alive 6 months after randomization.","definition_or_measurement_approach":"Proportion of randomized patients alive and progression-free at 6 months."}
• {"endpoint_text":"- Incidence and severity of TEAEs (NCI CTCAE v5.0).","definition_or_measurement_approach":"Treatment-emergent adverse events (TEAEs) incidence and severity graded by NCI CTCAE v5.0."}
• {"endpoint_text":"- Incidence of dose interruptions and treatment discontinuation.","definition_or_measurement_approach":"Counts and proportions of participants with dose interruptions and those who discontinue treatment."}
• {"endpoint_text":"- Change from baseline in select vital signs and clinical laboratory parameters.","definition_or_measurement_approach":"Change from baseline measures for selected vital signs and laboratory parameters at prespecified timepoints."}
• {"endpoint_text":"- ORR, defined as above.","definition_or_measurement_approach":"Objective Response Rate as defined in primary endpoints (per RECIST v1.1)."}
• {"endpoint_text":"- PFS rate at 12 months, defined as above.","definition_or_measurement_approach":"Proportion of patients alive and progression-free at 12 months after randomization."}
• {"endpoint_text":"- OS rate at 12 and 24 months, defined as the proportion of patients who are alive 12 and 24 months after randomization.","definition_or_measurement_approach":"Proportions of participants alive at 12 months and at 24 months post-randomization."}
• {"endpoint_text":"- TTCtx, defined as the time from randomization until the start date of chemotherapy or death from any cause (whichever occurs first).","definition_or_measurement_approach":"Time to start of subsequent chemotherapy (TTCtx): time from randomization to start date of chemotherapy or death."}
• {"endpoint_text":"- TTCD in pain presence and interference, defined as the time from randomization to the first documentation of a ≥10-point increase from baseline in the EORTC QLQ-C30 pain domain linearly transformed pain scale score held for 2 consecutive timepoints, or a ≥10-point increase followed by death attributable to cancer progression with 28 days from the last assessment.","definition_or_measurement_approach":"Time to confirmed deterioration (TTCD) in EORTC QLQ-C30 pain domain: first documented ≥10-point increase from baseline maintained at 2 consecutive assessments or ≥10-point increase followed by death within 28 days."}
• {"endpoint_text":"- TTCD in physical functioning (PF), role functioning (RF), and Global Health Status/quality of life (GHS/QoL), defined as the time from randomization to the first documentation of a ≥10 point decrease from baseline in the EORTC QLQ-C30 linearly transformed PF scale score, RF scale score, or GHS/QoL scale score, respectively, held for 2 consecutive timepoints, or a ≥10-point decrease followed by death attributable to cancer progression with 28 days from the last assessment.","definition_or_measurement_approach":"TTCD in EORTC QLQ-C30 domains PF, RF, and GHS/QoL: first documented ≥10-point decrease from baseline maintained over 2 consecutive assessments or followed by death within 28 days."}
• {"endpoint_text":"- Tumor-response endpoints defined as above but assessed according to iRECIST (ie, iPFS, iORR, iDOR, iCBR, and iPFS rate at 6 and 12 months).","definition_or_measurement_approach":"Immune-related tumor-response endpoints using iRECIST: iPFS, iORR, iDOR, iCBR and iPFS rates at specified timepoints."}
• {"endpoint_text":"- TTD in the pain and swallowing multi-item scales of the QLQ H&N35.","definition_or_measurement_approach":"Time to deterioration (TTD) in multi-item QLQ-H&N35 pain and swallowing scales: time to clinically meaningful worsening per instrument definitions."}
• {"endpoint_text":"- Mean scores and mean change from baseline scores in function (physical, role, cognitive, emotional, and social), GHS/QoL, and disease-and treatment-related symptoms, as assessed through use of the EORTC QLQ C30 and QLQ-H&N35 and EQ-5D-5L scales at specified timepoints.","definition_or_measurement_approach":"Patient-reported outcomes: mean scores and changes from baseline on EORTC QLQ-C30, QLQ-H&N35 and EQ-5D-5L at prespecified visits."}
• {"endpoint_text":"- Presence, frequency of occurrence, severity, and/or degree of interference with daily function of selected symptomatic treatment toxicities (ie, nausea, diarrhea, fatigue, rash, itching), as assessed through use of the NCI PRO CTCAE.","definition_or_measurement_approach":"Patient-reported symptomatic toxicities assessed by NCI PRO-CTCAE: presence, frequency, severity and interference with daily function."}
• {"endpoint_text":"- INBRX-106 concentration at prespecified timepoints and PK parameters such as Cmax, Ctrough, AUC, Vd, CL, and t1/2, as the data permit.","definition_or_measurement_approach":"Pharmacokinetics of INBRX-106: concentrations at prespecified times and derived PK parameters (Cmax, Ctrough, AUC, Vd, CL, t1/2) as data allow."}
• {"endpoint_text":"- Incidence of ADAs and neutralizing antibodies against INBRX-106.","definition_or_measurement_approach":"Immunogenicity assessments: incidence of anti-drug antibodies (ADAs) and neutralizing antibodies to INBRX-106."}
• {"endpoint_text":"- Relationship between biomarkers in blood, plasma, serum, PBMCs, and/or tumor tissue with efficacy, safety, PK, disease biology, or other biomarker endpoints.","definition_or_measurement_approach":"Exploratory biomarker analyses correlating biomarkers from blood/plasma/serum/PBMCs/tumor tissue with efficacy, safety, PK and other endpoints."}

France

Earliest CTIS Part Ii Submission Date

17-12-2024

Latest Decision Or Authorization Date

10-09-2025

Processing Time Days

267

Number Of Sites

5

Number Of Participants

28

Poland

Earliest CTIS Part Ii Submission Date

06-12-2024

Latest Decision Or Authorization Date

12-09-2025

Processing Time Days

280

Number Of Sites

3

Number Of Participants

14

Romania

Earliest CTIS Part Ii Submission Date

09-12-2024

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

276

Number Of Sites

4

Number Of Participants

24

Italy

Earliest CTIS Part Ii Submission Date

29-11-2024

Latest Decision Or Authorization Date

09-09-2025

Processing Time Days

284

Number Of Sites

4

Number Of Participants

19

Belgium

Earliest CTIS Part Ii Submission Date

06-12-2024

Latest Decision Or Authorization Date

08-09-2025

Processing Time Days

276

Number Of Sites

4

Number Of Participants

18

Spain

Earliest CTIS Part Ii Submission Date

03-10-2024

Latest Decision Or Authorization Date

08-10-2025

Processing Time Days

370

Number Of Sites

10

Number Of Participants

48

Bulgaria

Earliest CTIS Part Ii Submission Date

03-01-2025

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

493

Number Of Sites

5

Number Of Participants

24

Primary sponsor

Full Name

Inhibrx Biosciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Third parties

• {"country":"Slovakia","full_name":"SanaClis s.r.o.","duties_or_roles":"sponsorDuties codes: 1, 12","organisation_type":"Pharmaceutical company"}