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

Inhibrx Biosciences, Inc

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Solid Tumor

Melanoma

Gastric Cancer

Urothelial Carcinoma

Resectable Non-Small-Cell Lung Cancer

Renal Cell Carcinoma

Head and Neck Cancer

Non-Small Cell Lung Cancer

Treatments

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

Drug: Cisplatin 75mg/m2

Drug: Gemcitabine (1000 mg/m2)

Drug: Carboplatin AUC-5

Drug: pembrolizumab 400 mg

Drug: Paclitaxel 200mg/m2

Drug: Nab paclitaxel 100mg/m2

Drug: Carboplatin AUC-6

Drug: Pemetrexed 500 mg/m2

Study type

Interventional

Funder types

Industry

Identifiers

NCT04198766

Ph 1 Ph 2 INBRX-106

KEYNOTE A99 and MK-3475-A99 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment

340 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Select 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.
For Cohort F8, subjects must have previously untreated, histologically confirmed Stage II, IIIA or IIIB (T3-4N2) NSCLC. Lymph node disease requires histologic confirmation, while T3 disease requires only radiographic documentation. Subjects need to be able to undergo planned surgery.
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). For Cohort F8, any TPS (including 0%) is acceptable.
Adequate hematologic, coagulation, hepatic and renal function and ECOG score as defined per protocol.

Select Exclusion Criteria:

Prior exposure to OX40 agonists. Exposure to anti-PD-1 and/or anti PD-L2 CPIs or an agent targeting other co-stimulatory T-cell receptor pathways.
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.
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, viral myocarditis, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months prior to enrollment on this trial; 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 12 weeks 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 design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Single Blind

340 participants in 15 patient groups

Part 1 INBRX-106 Escalation (Not Recruiting)

Experimental group

Description:

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

Treatment:

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

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

Experimental group

Description:

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

Treatment:

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

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

Experimental group

Description:

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

Treatment:

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

Part 2 (Cohort C3) INBRX-106 Escalation in NSCLC (Not Recruiting)

Experimental group

Description:

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

Treatment:

Drug: pembrolizumab 200 mg

Part 4 (Cohort F3a) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (Not Recruiting)

Experimental group

Description:

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.

Treatment:

Drug: pembrolizumab 400 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

Part 4 (Cohort F3b) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (Not Recruiting)

Experimental group

Description:

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.

Treatment:

Drug: pembrolizumab 400 mg

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

Part 4 (Cohort F3c) Pembrolizumab Expansion Arm (Not Recruiting)

Active Comparator group

Description:

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.

Treatment:

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

Part 4 (Cohort F3d) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (Not-Recruiting)

Experimental group

Description:

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.

Treatment:

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

Part 4 (Cohort F4) INBRX-106 Expansion in Combination with pembrolizumab (Not Recruiting)

Experimental group

Description:

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.

Treatment:

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

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

Experimental group

Description:

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

Treatment:

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

Part 4 (Cohort F6) INBRX-106 Expansion with pembrolizumab in Uveal Melanoma (Not Recruiting)

Experimental group

Description:

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

Treatment:

Drug: Pemetrexed 500 mg/m2

Drug: Carboplatin AUC-5

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

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

Experimental group

Description:

This Arm is no longer recruiting. 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

Treatment:

Drug: Pemetrexed 500 mg/m2

Drug: Cisplatin 75mg/m2

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

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

Experimental group

Description:

Treatment:

Drug: Nab paclitaxel 100mg/m2

Drug: Carboplatin AUC-6

Drug: Paclitaxel 200mg/m2

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

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

Experimental group

Description:

This Arm is no longer recruiting. 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

Treatment:

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody

Part 4(Cohort F8)INBRX-106 with pembrolizumab, cisplatin and gemcitabine or pemetrexed in NSCLC

Experimental group

Description:

Subjects with resectable Stage II, IIIA or IIIB (T3-4N2) NSCLC , any PD-L1 TPS will receive neoadjuvant treatment with INBRX-106 0.1 mg/kg, 200 mg pembrolizumab, cisplatin 75 mg/m2 (dosed Day 1 only) with gemcitabine 1000 mg/m2 (dosed on Days 1 and 8) for patients with squamous cell NSCLC given every 3 weeks OR neoadjuvant treatment with INBRX-106 0.1 mg/kg, 200 mg pembrolizumab, cisplatin 75 mg/m2 with pemetrexed 500 mg/m2 for patients with non-squamous cell NSCLC given every 3 weeks. Carboplatin AUC5 (dosed on Day 1 only) can be substituted for Cisplatin following Cycle 1 at the Investigator's discretion and per protocol and due to cisplatin-related toxicity. Neoadjuvant treatment will be given for up to 4 cycles followed by surgery (lobectomy, bilobectomy or pneumonectomy). After surgery, all patients will receive adjuvant treatment consisting of INBRX-106 0.1 mg/kg, 200 mg pembrolizumab given every 3 weeks for up to 13 cycles.

Treatment:

Drug: Pemetrexed 500 mg/m2

Drug: Gemcitabine (1000 mg/m2)

Drug: Carboplatin AUC-5

Drug: Cisplatin 75mg/m2

Drug: pembrolizumab 200 mg

Drug: INBRX-106 - Hexavalent OX40 agonist antibody