MPDL3280A + Chemoradiation for Lung Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunostimulants, Immunosuppressants

Disqualifiers: Metastasis, Liver disease, Autoimmune, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 6-7 weeks

52 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to learn about the safety of adding MDPL3280A to standard chemotherapy (a combination of carboplatin and paclitaxel) and radiation in patients with lung cancer. You are being asked to take part in this study because you have non-small cell lung cancer (NSCLC) that is unresectable (cannot be removed by surgery) and has not spread. This is an investigational study. MPDL3280A is not FDA approved or commercially available. It is currently being used for research purposes only. Paclitaxel, carboplatin, and the radiation therapy are all FDA approved for the treatment of lung cancer. The use of these drugs in combination is considered investigational. Up to 40 participants will be enrolled in this study. All will take part at MD Anderson.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting the study. Specifically, you must not have taken any systemic immunostimulatory agents within 6 weeks or systemic immunosuppressive medications within 2 weeks prior to the start of the trial. If you are on these types of medications, you may need to stop them before participating.

What data supports the effectiveness of the treatment MPDL3280A + Chemoradiation for Lung Cancer?

Research shows that combining paclitaxel and carboplatin with radiation therapy has produced promising results in treating advanced non-small cell lung cancer (NSCLC), improving survival rates compared to radiation alone. ^{1 2 3 4 5}

Is the combination of MPDL3280A and chemoradiation generally safe for humans?

Research indicates that combining radiotherapy with PD-(L)1 inhibitors, like MPDL3280A, can be safe, though there is a risk of lung inflammation (pneumonitis). Stereotactic body radiation therapy (SBRT) combined with chemotherapy has shown generally mild side effects, with some cases of more severe lung toxicity. ^{6 7 8 9 10}

What makes the MPDL3280A + Chemoradiation treatment for lung cancer unique?

This treatment combines MPDL3280A, a novel immunotherapy drug, with traditional chemoradiation (chemotherapy and radiation therapy) to potentially enhance the body's immune response against lung cancer, offering a new approach compared to standard treatments that typically do not include immunotherapy. ^{3 4 11 12 13}

Research Team

Steven H. Lin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with non-small cell lung cancer that can't be removed by surgery and hasn't spread. Participants must have good organ function, agree to use contraception if they can have children, and be willing to follow the study rules. People with severe allergies, certain other cancers or diseases, recent treatments or surgeries, infections like HIV/hepatitis B/C, or who are pregnant/breastfeeding cannot join.

Inclusion Criteria

Ability and willingness to comply with the requirements of the study protocol

For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception and to continue its use for a specified period after the last dose of MPDL3280A

My blood clotting tests are within normal limits, and I'm not on strong blood thinners.

Exclusion Criteria

I have not had severe infections in the last 4 weeks.

I have a significant liver condition, such as hepatitis or cirrhosis.

I haven't had major surgery in the last 28 days and don't expect to need one during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard chemotherapy and radiation for 6-7 weeks, with MPDL3280A administered weekly

6-7 weeks

Weekly visits for chemotherapy and radiation

Rest Period

Participants have a rest period with no chemotherapy or radiation; Group 2 receives 1 dose of MPDL3280A

3-8 weeks

Consolidation

Participants receive MPDL3280A in addition to chemotherapy for 2 cycles

6 weeks

Visits during Weeks 1-3 and Weeks 4-6

Maintenance

Participants continue to receive MPDL3280A alone for up to 1 year

up to 1 year

Every 2 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

Every 2-4 months for up to 2 years, then every 4-6 months

Treatment Details

Interventions

• Carboplatin
• MPDL3280A
• Paclitaxel
• Radiation Therapy

Trial Overview The trial tests adding MPDL3280A (not yet FDA approved) to standard chemo (carboplatin and paclitaxel) plus radiation therapy in treating lung cancer. The combination's safety is being studied in up to 40 participants at MD Anderson Cancer Center.

Participant Groups

Group I: Group 2: MPDL3280A + Chemotherapy + Radiation Experimental Treatment 4 Interventions

Participants receive MPDL3280A, standard chemotherapy, and radiation therapy for 6-7 weeks. This will be followed by a rest period of 3-4 weeks, during which time participant receives 1 dose of MPDL3280A but no chemotherapy or radiation. Consolidation Phase: After the rest period, participants receive MPDL3280A in addition to chemotherapy for 2 cycles. Maintenance Phase: After completing the consolidation period, participants continue to receive MPDL3280A alone for up to 1 year.

Group II: Group 1: Chemotherapy + Radiation Experimental Treatment 4 Interventions

Participants receive standard chemotherapy and radiation for 6-7 weeks, followed by a 3-4 week rest period when they receive no chemotherapy or radiation. Consolidation Phase: After the rest period, participants receive MPDL3280A in addition to chemotherapy for 2 cycles. Maintenance Phase: After completing the consolidation period, participants continue to receive MPDL3280A alone for up to 1 year.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

Combined chemotherapy with paclitaxel and carboplatin alongside thoracic radiation therapy has shown a clear survival benefit for patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), as demonstrated in randomized trials and meta-analyses.

Ongoing and planned multicenter studies aim to refine treatment regimens and improve both local and systemic control of NSCLC, highlighting the need for a multidisciplinary approach to effectively manage this systemic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. Belani, CP.[2015]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

In a phase II clinical trial involving 40 patients with locally advanced non-small-cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and radiation therapy resulted in a high overall response rate of 75.7% and a median overall survival of 20.5 months.

While the treatment was effective, it also led to significant toxicity, with 46% of patients experiencing grade 3 or 4 esophagitis, although late esophageal complications were rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. Choy, H., Akerley, W., Safran, H., et al.[2017]

In a study of 96 lung cancer patients who received thoracic radiotherapy (TRT) after PD-(L)1 inhibitor treatment, nearly 49% developed symptomatic treatment-related pneumonitis, indicating a significant safety concern with this treatment sequence.

Independent risk factors for developing pneumonitis included pulmonary emphysema and lung V20 exposure, highlighting the need for careful patient selection and monitoring when using TRT after PD-(L)1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. Chen, Y., Liu, X., Huang, Z., et al.[2022]

The combination of NBTXR3, high-dose radiation, low-dose radiation, and immune checkpoint inhibitors significantly improved survival rates in a mouse model of anti-PD1-resistant metastatic lung cancer, increasing survival from 0% to 50%.

This treatment enhanced the immune response by increasing CD8 T-cell infiltration and reducing regulatory T cells in the tumors, suggesting that NBTXR3 may help overcome resistance to anti-PD1 therapy by promoting a stronger antitumor immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model. Hu, Y., Paris, S., Barsoumian, H., et al.[2022]

A retrospective study of 40 patients with hilar or mediastinal non-small cell lung cancer (NSCLC) treated with SBRT showed promising results, with a median overall survival of 22.7 months and a two-year local control rate of 87.7%.

The study indicated that SBRT is a safe treatment option, with only a small number of patients experiencing acute or late severe side effects, suggesting that the alternative dose-fractionation schemes used may improve safety without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for isolated hilar and mediastinal non-small cell lung cancers. Horne, ZD., Richman, AH., Dohopolski, MJ., et al.[2018]

A phase II study involving 32 patients with advanced non-small cell lung cancer showed that combining paclitaxel with carboplatin and radiotherapy is feasible and has acceptable toxicity levels, with no grade 4 toxicities reported.

While some patients experienced grade 3 neutropenia and mucositis, the study indicates that this combined treatment approach could improve outcomes, and further research is needed to optimize dosages and treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease. Belani, CP., Aisner, J., Bahri, S., et al.[2015]

Combination therapy using paclitaxel with carboplatin and radiation shows promise as a safer and more effective treatment for non-small cell lung cancer compared to the standard regimen of etoposide and cisplatin.

The use of paclitaxel, a novel taxane drug, in conjunction with radiation therapy may enhance local control of the cancer and improve overall response rates, suggesting a potential advancement in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. Choy, H., Akerley, W., DeVore, RF.[2015]

References

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

Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. [2015]

2. China pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. [2010]

3. Ireland pubmed.ncbi.nlm.nih.gov

Phase I study of concurrent real-time tumor-tracking thoracic radiation therapy with paclitaxel and carboplatin in locally advanced non-small cell lung cancer. [2015]

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

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. [2017]

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

A phase I/II trial of paclitaxel, carboplatin, and gemcitabine in untreated patients with advanced non-small cell lung cancer. [2022]

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

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for isolated hilar and mediastinal non-small cell lung cancers. [2018]

9. Ireland pubmed.ncbi.nlm.nih.gov

External validation of pulmonary radiotherapy toxicity models for ultracentral lung tumors. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Feasibility of Stereotactic Body Radiation Therapy on Unresectable Stage III NSCLC with Peripheral Primary Tumor: A Prospective Study (GFPC 01-14). [2021]

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

Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease. [2015]

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

The current state of paclitaxel and radiation in the combined-modality therapy of non-small cell lung cancer. [2019]

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

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. [2015]