Bone Cancer > Pembrolizumab

Pembrolizumab + Pemetrexed for Bone Cancer

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Saint John's Cancer Institute

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Primary Objective: 1. To determine objective response rate (ORR) according to RECIST v1.1 of pembrolizumab and high-dose pemetrexed in the treatment of patients with chordoma until disease progression. The OOR will be investigator assessed. Secondary Objectives: 1. To describe the adverse events associated with administering pembrolizumab and high-dose pemetrexed combination treatment. 2. To determine disease control rate based on imaging and overall survival. 3. To determine median PFS and PFS rates at 6, 9, 12, and 18 months. 4. To evaluate changes in volumetric tumor measurements based on imaging. 5. To determine the effects of combination treatment on quality of life, assessed by the EORTC-QLQ-C30 questionnaire. 6. To assess tumor evolution over time in patients with chordoma based on imaging, and molecular profiling. 7. To assess the pharmacodynamic effects of treatment in blood. Exploratory Objective: 1. To explore the relationship between molecular phenotype and patient response.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to interrupt non-steroidal anti-inflammatory drugs (NSAIDs) around the time of Pemetrexed administration.

What data supports the effectiveness of the drugs Pembrolizumab and Pemetrexed for bone cancer?

Research shows that Pembrolizumab, when used for lung cancer that has spread to the bones, can significantly improve both lung tumors and bone metastasis. Additionally, Pembrolizumab combined with Pemetrexed has been effective in improving survival rates in lung cancer patients, suggesting potential benefits for bone cancer treatment.

^{1 2 3 4 5}

How is the drug combination of Pembrolizumab and Pemetrexed unique for bone cancer treatment?

The combination of Pembrolizumab and Pemetrexed is unique for bone cancer treatment because Pembrolizumab is an immunotherapy that enhances the body's immune response against cancer cells, and it has shown promise in treating bone metastasis in other cancers like non-small cell lung cancer. This approach is different from traditional chemotherapy as it targets the immune system rather than directly attacking cancer cells.

^{1 5 6 7 8}

Eligibility Criteria

This trial is for patients with chordoma, a type of bone cancer, who have seen their disease progress. Participants should meet certain health standards to be eligible but specific inclusion and exclusion criteria are not listed.

Inclusion Criteria

I have been diagnosed with chordoma.

I am fully active or can carry out light work.

I am either not able to have children or agree to use effective birth control during and after the study.

Exclusion Criteria

I have or had lung inflammation not caused by an infection.

I have fluid buildup that can't be managed with drainage.

I have an active Hepatitis B or C infection.

I have received an organ or tissue transplant from another person.

I have a history of serious heart conditions.

I have another cancer that is getting worse or was treated in the last 3 years.

I do not have any active infections needing IV antibiotics, or any fungal or viral infections.

I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

I have a severe health condition that could affect my participation in the study.

I am pregnant or nursing.

Participant Groups

The study tests the effectiveness of Pembrolizumab combined with high-dose Pemetrexed in treating chordoma. It aims to measure how well tumors respond, control rate of the disease, overall survival time, progression-free survival at various intervals, tumor size changes over time, quality of life impacts and molecular changes in tumors.

Group I: Single Arm Experimental Treatment 2 Interventions

Eligible patients will receive pembrolizumab 200 mg IV infusion on Day 1 of each 21-day cycle, and pemetrexed 900 mg/m2 by intravenous (IV) infusion on Day 1 of each 21-day treatment cycle and supportive medications (folic acid, vitamin B12, and dexamethasone).

Find A Clinic Near You

Research locations nearby Select from list below to view details:

Providence Saint John's Health Center Santa Monica, CA

Who is running the clinical trial?

Saint John's Cancer Institute Lead Sponsor

Chordoma Foundation Collaborator

References

1. Greece pubmed.ncbi.nlm.nih.gov

Complete Response of Bone Metastasis in Non-small Cell Lung Cancer With Pembrolizumab: Two Case Reports. [2021] To report two cases in which treatment with pembrolizumab for advanced non-small cell lung cancer (NSCLC) with bone metastasis of the long bone of the lower extremity in a state of impending fracture significantly ameliorated both lung tumor and bone metastasis.

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

Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. [2020] Pembrolizumab plus pemetrexed-platinum led to superior overall survival and progression-free survival, and a higher proportion of patients with a confirmed complete or partial response over placebo plus pemetrexed-platinum in the KEYNOTE-189 study. We aimed to evaluate prespecified exploratory patient-reported outcomes (PROs) in patients in KEYNOTE-189.

3. England pubmed.ncbi.nlm.nih.gov

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. [2022] In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed-platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed-platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed-platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab.

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

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. [2023] In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown.

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. [2018] This review describes trials evaluating the monoclonal antibody pembrolizumab (an immunotherapy that blocks the interaction between programmed death-1 and programmed death-ligand 1 and 2 [PD-L1/PD-L2]) as first-line therapy for advanced non-small-cell lung cancer (NSCLC). In the Phase III KEYNOTE-024 study, pembrolizumab monotherapy significantly improved progression-free survival (primary end point) and overall survival, and was associated with fewer adverse events compared with platinum-based chemotherapy in patients with NSCLC with PD-L1 expression on ≥50% of tumor cells. In cohort G of the Phase I/II KEYNOTE-021 study, pembrolizumab plus pemetrexed and carboplatin significantly improved objective response rate (primary end point) and progression-free survival versus pemetrexed and carboplatin alone, and had manageable toxicity in patients with nonsquamous NSCLC. These results have changed first-line management of advanced NSCLC.

6. Germany pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. [2022] To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma.

7. Switzerland pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. [2022] Pembrolizumab is a humanized monoclonal antibody which serves to enhance the antitumor immune response by targeting programmed cell death 1 receptor. The use of pembrolizumab plus carboplatin/pemetrexed combination therapy results in improvement in overall survival and progression-free survival rates for non-small cell lung cancer (NSCLC) patients as compared to chemotherapy alone. However, numerous immune-mediated toxicities of pembrolizumab have been reported.

8. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023] Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.