INBRX-106 + Pembrolizumab for Lung Cancer

Recruiting at 48 trial locations

Overseen By David Berz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Inhibrx Biosciences, Inc

Must not be taking: OX40 agonists, Immunosuppressants

Disqualifiers: Hematologic malignancies, CNS metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

333 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for certain types of lung cancer and other advanced solid tumors. The main goal is to determine if the combination of INBRX-106 (an experimental treatment) and pembrolizumab (an existing cancer medication) is safe and to establish the best dose for future studies. It targets individuals whose cancer has advanced despite previous treatments or for whom no current treatments are available. Those with non-small cell lung cancer (NSCLC) or another solid tumor unresponsive to standard therapies might find this trial suitable. As a Phase 1, Phase 2 trial, the study focuses on understanding how the treatment works in participants and measuring its effectiveness in an initial group, offering a chance to be among the first to benefit from this innovative approach.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken any investigational or approved anticancer drugs within 4 weeks before starting the trial, and certain other medications may have exceptions as defined in the protocol.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that INBRX-106, when combined with pembrolizumab (Keytruda), is generally well tolerated. In earlier studies, most side effects were mild to moderate and related to the immune system, suggesting the treatment is relatively safe for participants. Pembrolizumab, already approved for treating various cancers, provides an additional layer of known safety. While these findings are promising, each person's experience may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment involving INBRX-106 combined with pembrolizumab for lung cancer because it brings a novel approach to tackling tumors. Unlike current standard treatments that often focus on targeting PD-1 or PD-L1 pathways, INBRX-106 is a hexavalent OX40 agonist, which means it can potentially enhance the immune system's ability to attack cancer cells by activating the OX40 pathway. This combination aims to amplify the immune response in non-small cell lung cancer (NSCLC) patients, potentially offering improved efficacy over existing therapies. By integrating INBRX-106 with pembrolizumab, which is already known for its immune checkpoint inhibition, this treatment could offer a more robust and comprehensive attack on cancer cells.

What evidence suggests that this trial's treatments could be effective for lung cancer?

This trial will evaluate the combination of INBRX-106 and pembrolizumab (Keytruda) for treating non-small cell lung cancer (NSCLC) and other solid tumors. Studies have shown that INBRX-106 activates a molecule called OX40, which strengthens the immune system's ability to fight tumors. This activation enhances the function of T-cells, crucial for battling cancer. Early findings suggest that combining INBRX-106 with pembrolizumab is generally well tolerated, with mostly mild or moderate side effects. Research indicates that this combination shows early promise in treating solid tumors, such as NSCLC. While detailed effectiveness data is still being gathered, the combination aims to target cancer cells by boosting the body's immune response, offering hope for better outcomes. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Lead

Principal Investigator

Inhibrx Biosciences, Inc

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer who have tried at least one standard of care treatment. They must not have certain gene mutations (EGFR, ALK) or prior exposure to OX40 agonists and should be free of serious heart conditions, active infections, and immune-related side effects from previous therapies.

Inclusion Criteria

Has your disease progressed or come back despite treatment?

My non-squamous NSCLC lacks EGFR mutations and ALK rearrangements.

Do you have locally advanced or metastatic non-small cell lung cancer?

Exclusion Criteria

I have previously been treated with OX40 agonists.

I do not have recent severe heart issues or uncontrolled high blood pressure.

Has your tumor tested positive for the EGFR mutations and/or the ALK gene? Check your biomarker test results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors, either as a single agent or in combination with pembrolizumab

Variable, based on dose escalation needs

Treatment

Participants receive INBRX-106 and pembrolizumab, with or without chemotherapy, in various dosing regimens across multiple cohorts

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• INBRX-106
• Pembrolizumab

Trial Overview The study tests INBRX-106 alone and combined with Pembrolizumab (keytruda) in different doses to find the safest and most effective amount for treating solid tumors.

How Is the Trial Designed?

Group I: Part 4(Cohort F7c)INBRX-106 Expansion with pembrolizumab, (Nab)-paclitaxel and carboplatin in NSCLC Experimental Treatment 2 Interventions

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

Group II: Part 4 (Cohort F7b) INBRX-106 Expansion with pembrolizumab, pemetrexed and cisplatin in NSCLC Experimental Treatment 5 Interventions

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 75mg/m2 cisplatin IV every 3 weeks

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

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

Group IV: Part 4 (Cohort F6) INBRX-106 Expansion with pembrolizumab in Uveal Melanoma (Not Recruiting) Experimental Treatment 4 Interventions

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

Group V: Part 4 (Cohort F5)INBRX-106 Expansion with pembrolizumab in MSI/TMB-high/MMRd tumors Not Recuriting Experimental Treatment 2 Interventions

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

Group VI: Part 4 (Cohort F4) INBRX-106 Expansion in Combination with pembrolizumab Experimental Treatment 2 Interventions

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. Only NPC is currently enrolling.

Group VII: Part 4 (Cohort F3d) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (concurrent) Experimental Treatment 1 Intervention

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.

Group VIII: Part 4 (Cohort F3b) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (Not Recruiting) Experimental Treatment 3 Interventions

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.

Group IX: Part 4 (Cohort F3a) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (Not Recruiting) Experimental Treatment 2 Interventions

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.

Group X: Part 3 INBRX-106 Escalation in Combination with pembrolizumab (Not Recruiting) Experimental Treatment 2 Interventions

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

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

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

Group XII: Part 2 (Cohort C3) INBRX-106 Escalation in NSCLC (Not Recruiting) Experimental Treatment 1 Intervention

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

Group XIII: Part 1 INBRX-106 Escalation (Not Recruiting) Experimental Treatment 1 Intervention

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

Group XIV: Part 4 (Cohort F3c) Pembrolizumab Expansion Arm (Not Recruiting) Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Inhibrx Biosciences, Inc

Lead Sponsor

Trials

9

Recruited

1,700+

Inhibrx, Inc.

Lead Sponsor

Trials

9

Recruited

1,700+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04198766

NCT04198766 | Study of INBRX-106 and ... 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS6109

HexAgon-HN: Phase 2/3, randomized study of the ... A phase 2/3, randomized study evaluating INBRX-106 + pembro vs pembro alone as first-line treatment for R/M HNSCC with a PD-L1 CPS of ≥20.

3. inhibrxbiosciences.investorroom.com inhibrxbiosciences.investorroom.com/2022-01-04-Inhibrx-Announces-Initial-Phase-1-Dose-Escalation-Results-for-INBRX-106,-a-Novel-Hexavalent-OX40-Agonist,-in-Combination-with-Keytruda-R-Pembrolizumab-Along-with-Updated-Single-Agent-Data

Inhibrx Announces Initial Phase 1 Dose Escalation Results for ... INBRX-106 in combination with Keytruda was observed to be well tolerated, with predominantly mild or moderate immune-related toxicities noted.

4. healthpartners.com healthpartners.com/institute/research/studies/inbrx-106-an-open-label-multicenter-first-in-human-dose-escalation-multicohort-phase-1-2-study-of-inbrx-106-and-inbrx-106-in-combination-with-pembrolizumab-in-subjects-with-locally-advanced-or-m/

INBRX-106: An Open-Label, Multicenter, First-in Human ... The purpose of the study is to determine the safety and tolerability of the study drug INBRX-106. INBRX-106 works by activating OX40, which is a stimulant for ...

5. inhibrx.com inhibrx.com/wp-content/uploads/2024/08/inhibrx-bio-investor-deck-august-2024.pdf

INHIBRX Investor Presentation T-cells versus bi-valent OX40 mAbs. INBRX-106, but a not bivalent OX40 mAb, reduces regulatory T-cell (Treg) mediated suppression of effector ...

6. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A844

748 Phase 1/2 study of the hexavalent OX40 agonist ... A murine INBRX-106 surrogate showed antitumor activity in mouse tumor models resistant or responsive to checkpoint inhibitors (CPIs).

7. inhibrx.com inhibrx.com/wp-content/uploads/2023/08/Inhibrx-Presentation-August-2023.pdf

INBX Investor Presentation The Phase 1 study data provide emerging evidence of a dose-dependent increase in INBRX-101 lung exposure. ... Phase 1/2 study of single agent INBRX-106 and INBRX- ...