Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

Study Purpose

This is a Phase 1/2, open-label, non-randomized, 4-part trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda®). KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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Inclusion Criteria:

- Males or females aged ≥18 years.

- Parts 1 and 3 (escalation cohorts): Subjects with locally advanced or metastatic non resectable solid tumors, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.

- Part 2 (single-agent expansion cohort): Subjects with NSCLC, melanoma, HNSCC, G/GEA, RCC, or TCC, with histologically confirmed, locally advanced or metastatic, non-resectable disease, which has progressed despite all standard therapies including CPI or for whom no standard or clinically acceptable therapy exists.

- Part 4 (expansion cohorts in combination with pembrolizumab, with or without chemotherapy): Subjects with melanoma (all types), HNSCC, G/GEA, RCC, TCC, NSCLC, or MSI-high, TMB-high, MMR-deficient tumors, with histologically confirmed, locally advanced or metastatic, non resectable disease, which is either CPI-naive (melanoma, HNSCC, NPC) or progressed despite all standard therapies including CPI (NSCLC, RCC, TCC, uveal melanoma, MSI-high, TMB-high, or MMR-deficient solid tumors) or for whom no standard or clinically acceptable therapy exists.

- For Cohort F3 (NSCLC), subjects may have progressed on no more than 2 lines of standard therapy that must include at least one PD-1/L1 regimen.

- For Cohort F4 (HNSCC and NPC), subjects may be previously treated with no more than 1 prior chemotherapy regimen in metastatic setting.

Prior PD-1/L1 in curative (neo-adjuvant/adjuvant) setting is allowed only if completed >/= 6 months prior to progression to local recurrence or metastatic disease.

- All subjects with non-squamous NSCLC must have documentation of absence of tumor activating EGFR mutations and absence of ALK gene rearrangements.

- PD-L1 by IHC (22C3): Parts 1 and 3: IHC optional.

Part 2: IHC result mandatory but any score allowed. Combined Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥50% for NSCLC; for TMB-high tumors, any TPS% is allowed). Part 4: Combined Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥50% for NSCLC; for TMB-high tumors, any TPS% is allowed).

- Adequate hematologic, coagulation, hepatic and renal function and ECOG score as defined per protocol.

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Exclusion Criteria:

- Prior exposure to OX40 agonists.

- Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug with certain exceptions.

- Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's lymphoma and multiple myeloma) - Prior or concurrent malignancies.

Exception: Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of INBRX-106.

- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

Exception: Subjects who are previously treated and are radiologically and clinically stable without the requirement for steroid treatment for at least 14 days prior to first dose of study treatment may be allowed study entry if certain criteria apply.

- Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy.

Some exceptions as defined per protocol apply.

- Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications.

Certain exceptions as defined in protocol apply.

- Diagnosis of immunodeficiency or treatment with systemic immunosuppressive medications within 7 days prior to the first dose of study drug.

Certain exceptions as defined in protocol apply.

- History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.

Exceptions as defined in protocol apply.

- Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications.

- Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months; left ventricular ejection fraction (LVEF) < 50%; New York Heart Association (NYHA) Class III or IV congestive heart failure; or uncontrolled hypertension; or oxygen saturation <92% on room air.

- Active, hemodynamically significant pulmonary embolism within 3 months prior to enrollment on this trial.

- Major surgery within 4 weeks prior to enrollment on this trial.

- Anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to the first dose of study drug.

- Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation.

- Additional in- and exclusion criteria per protocol.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04198766
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Inhibrx Biosciences, Inc
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Clinical Lead
Principal Investigator Affiliation	Inhibrx Biosciences, Inc
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Solid Tumor, Non-Small Cell Lung Cancer, Head and Neck Cancer, Melanoma, Gastric Cancer, Renal Cell Carcinoma, Urothelial Carcinoma

Arms & Interventions

Arms

Experimental: Part 1 INBRX-106 Escalation (Not Recruiting)

INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors.

Experimental: Part 3 INBRX-106 Escalation in Combination with pembrolizumab (Not Recruiting)

INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors.

Experimental: Part 2 (Cohorts C1/C2) INBRX-106 Escalation in Various Solid Tumor Types (Not Recruiting)

Subjects with melanoma (any type), head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma or MSI/TMB-high tumors that are relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106

Experimental: Part 2 (Cohort C3) INBRX-106 Escalation in NSCLC

Subjects with non-small cell carcinoma relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106

Experimental: Part 4 (Cohort F3a) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (alternating)

Subjects with non-small cell lung cancer will be treated with alternating dosing of INBRX-106 0.3 mg/kg Q6W and 400 mg pembrolizumab IV Q6W. This is one of the randomized cohorts.

Experimental: Part 4 (Cohort F3b) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC

Subjects with non-small cell lung cancer will be given a 0.3 mg/kg priming dose of INBRX-106 in cycle 1, followed by 0.1 mg/kg INBRX-106 and 200 mg pembrolizumab IV every 3 weeks in subsequent cycles. This is one of the randomized cohorts.

Active Comparator: Part 4 (Cohort F3c) Pembrolizumab Expansion Arm (Not Recruiting)

Subjects with non-small cell lung cancer will be treated with 200 mg pembrolizumab IV every 3 weeks. This is one of the randomized cohorts.

Experimental: Part 4 (Cohort F3d) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (concurrent)

Subjects with non-small cell lung cancer will be treated concurrently every 6 weeks with INBRX-106 0.1 mg/kg and 200 mg pembrolizumab IV every 3 weeks. This is one of the randomized cohorts.

Experimental: Part 4 (Cohort F4) INBRX-106 Expansion in Combination with pembrolizumab

Subjects with melanoma (any type), head and neck squamous cell carcinoma (non-nasopharyngeal) OR nasopharyngeal carcinoma, MSI-high, TMB-high or MMR-deficient tumors, will be treated with INBRX-106 in combination with 200mg pembrolizumab IV every 3 weeks.

Experimental: Part 4 (Cohort F5)INBRX-106 Expansion with pembrolizumab in MSI/TMB-high/MMRd tumors Not Recuriting

Subjects with solid tumors that have confirmed MSI-high, TMB-high or MMR-deficient states who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks

Experimental: Part 4 (Cohort F6) INBRX-106 Expansion with pembrolizumab in Uveal Melanoma

Subjects with ocular (uveal) melanoma who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks

Experimental: Part 4 (Cohort F7a) INBRX-106 Expansion with pembrolizumab, pemetrexed and carboplatin in NSCLC

Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and carboplatin AUC-5 IV every 3 weeks

Experimental: Part 4 (Cohort F7b) INBRX-106 Expansion with pembrolizumab, pemetrexed and cisplatin in NSCLC

Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and 75mg/m2 cisplatin IV every 3 weeks

Experimental: Part 4(Cohort F7c)INBRX-106 Expansion with pembrolizumab, (Nab)-paclitaxel and carboplatin in NSCLC

Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 200mg/m2 paclitaxel and carboplatin AUC-6 IV every 3 weeks OR INBRX-106, 200mg pembrolizumab, 100mg/m2 nab-paclitaxel (dosed Days 1,8 and 15 every cycle) and carboplatin AUC-6 IV every 3 weeks. Treating physician to determine if paclitaxel or nab-paclitaxel will be given

Interventions

Drug: - INBRX-106 - Hexavalent OX40 agonist antibody

The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).

Drug: - pembrolizumab 200 mg

pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.

Drug: - pembrolizumab 400 mg

pembrolizumab 400 mg by IV infusion given on Day 1 of alternating 21-day cycles (every 6 weeks)

Drug: - Carboplatin AUC-5

carboplatin AUC-5 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4

Drug: - Carboplatin AUC-6

carboplatin AUC-6 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4

Drug: - Pemetrexed 500 mg/m2

pemetrexed 500 mg/m2 by IV infusion given on Day 1 of each 21-Day cycle for up to 35 cycles

Drug: - Cisplatin 75mg/m2

cisplatin 75mg/m2 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4

Drug: - Paclitaxel 200mg/m2

paclitaxel 200mg/m2 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4

Drug: - Nab paclitaxel 100mg/m2

Nab paclitaxel 100mg/m2 by intravenous (IV) infusion, given on Days 1, 8 and 15 of each 21-day cycle of cycles 1-4

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

City of Hope, Duarte 5344147, California 5332921

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Recruiting

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City of Hope

Duarte 5344147, California 5332921, 91010

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