INBRX-106 + Pembrolizumab for Lung Cancer

Recruiting in Palo Alto (17 mi)

+23 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Inhibrx Biosciences, Inc

Must not be taking: OX40 agonists, Immunosuppressants

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

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug INBRX-106 + Pembrolizumab for lung cancer?

Pembrolizumab, one of the drugs in the treatment, has been shown to improve survival in patients with advanced non-small cell lung cancer (NSCLC) in several studies. It is approved for use in patients with certain types of lung cancer, demonstrating significant improvements in survival compared to chemotherapy. ^{1 2 3 4 5}

Is the combination of INBRX-106 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, and nausea. Serious side effects, such as pneumonitis (lung inflammation), have been reported in 1%-5% of patients. Always discuss potential risks with your healthcare provider. ^{1 2 4 6 7}

How is the drug INBRX-106 + Pembrolizumab unique for lung cancer treatment?

The combination of INBRX-106 and Pembrolizumab is unique because it pairs a novel investigational drug, INBRX-106, with Pembrolizumab, a well-established immune checkpoint inhibitor that targets the PD-1 pathway, potentially enhancing the immune system's ability to fight lung cancer. ^{1 2 3 4 5}

Research Team

Clinical Lead

Principal Investigator

Inhibrx Biosciences, Inc

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• INBRX-106 (Monoclonal Antibodies)
• Pembrolizumab (Checkpoint Inhibitor)

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.

Participant Groups

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

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

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

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 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.

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 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 (alternating) 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 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

Findings from Research

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, 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]

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]

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]

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, 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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. China 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]