Combination Therapy for Lung Cancer

Recruiting at 2 trial locations

Overseen By Lori Stravers

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Organ transplant, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

Non-Small Cell Lung Cancer (NSCLC) is one of the deadliest types of cancer. In lung cancer patients with a tumor that can be removed by surgery, adjuvant chemotherapy increases survival. Neoadjuvant therapy may have advantages such as, it may be more tolerable prior to surgery, earlier treatment may be more efficacious, and it can provide an indication of treatment response. Neoadjuvant treatment can provide pre- and post-treatment specimens for correlative analysis to better understand mechanisms of action and resistance. This pilot study will investigate the effects of neoadjuvant durvalumab plus platinum doublet chemotherapy and neoadjuvant durvalumab plus platinum doublet chemotherapy in combination with abequolixron (RGX-104), an LXR/ApoE agonist, in subjects with NSCLC who are scheduled to undergo surgical resection as part of their standard of care. The purpose of this study is to study how well using a combination of durvalumab, platinum doublet chemotherapy (carboplatin/abraxane or carboplatin/pemetrexed), and abequolixron treats non-small cell lung cancer before surgery. Durvalumab (a type of immunotherapy) and platinum doublet chemotherapy are drugs that are individually approved for use during the treatment of cancer. FDA (Food and Drug Administration) has not approved the combined use of these drugs in treating non-small cell lung cancer. Abequolixron is not FDA approved for the treatment of cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving other chemotherapy, investigational products, or biologic or hormonal therapy for cancer treatment, except for those mentioned in the trial.

Is the combination therapy for lung cancer generally safe in humans?

The combination therapy involving carboplatin has been studied in various trials and is generally considered to have an acceptable safety profile, though it can cause side effects like thrombocytopenia (low platelet count) and leukopenia (low white blood cell count). Other side effects may include nausea and vomiting, but significant kidney, ear, or nerve damage was not observed in these studies. ^{1 2 3 4 5}

How is the combination therapy of Carboplatin and Durvalumab unique for lung cancer treatment?

The combination of Carboplatin and Durvalumab (Imfinzi) for lung cancer is unique because it combines a chemotherapy drug (Carboplatin) with an immunotherapy drug (Durvalumab), which helps the immune system recognize and attack cancer cells. This approach is different from traditional chemotherapy alone, as it aims to enhance the body's natural defenses against cancer. ^{4 6 7 8 9}

What data supports the effectiveness of the drug combination therapy for lung cancer?

Research shows that combinations including pemetrexed and carboplatin have demonstrated effectiveness in treating advanced non-small-cell lung cancer (NSCLC), as seen in studies like PointBreak and PRONOUNCE. These studies highlight the potential of these drugs in improving outcomes for patients with this type of lung cancer. ^{6 10 11 12 13}

Who Is on the Research Team?

Jared Weiss, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with non-small cell lung cancer that can be surgically removed. They must weigh more than 40 kg, have a good performance status (able to carry out daily activities), and not be on other cancer treatments except those in the study.

Inclusion Criteria

I am fully active or can carry out light work.

My lung cancer is confirmed and surgery is recommended.

You weigh more than 40 kilograms.

Exclusion Criteria

I am not on any cancer treatments except those allowed in this study or hormone therapy for non-cancer reasons.

Concurrent enrollment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

You have had an organ transplant from another person.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant durvalumab plus platinum doublet chemotherapy and neoadjuvant durvalumab plus platinum doublet chemotherapy in combination with abequolixron (RGX-104)

Up to 120 days

Surgery

Surgical resection of the tumor is performed as part of the standard of care

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abequolixron
• Abraxane
• Carboplatin
• Durvalumab
• Pemetrexed

Trial Overview The study tests how well non-small cell lung cancer responds before surgery to durvalumab (immunotherapy) plus chemotherapy (carboplatin with abraxane or pemetrexed), and when combined with an experimental drug called abequolixron.

How Is the Trial Designed?

Group I: Neoadjuvant therapy Experimental Treatment 5 Interventions

Subjects with operable Non-Small Cell Lung Cancer received neoadjuvant durvalumab plus platinum doublet chemotherapy and neoadjuvant durvalumab plus platinum doublet chemotherapy in combination with abequolixron (RGX-104), an LXR/ApoE agonist.

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?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Rgenix, Inc.

Industry Sponsor

Trials

3

Recruited

260+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a phase III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., et al.[2023]

In a study involving 939 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed, carboplatin, and bevacizumab (PemCBev) did not show a significant improvement in overall survival compared to paclitaxel, carboplatin, and bevacizumab (PacCBev), with median overall survival times of 12.6 and 13.4 months, respectively.

However, PemCBev demonstrated a significantly better progression-free survival (6.0 months vs. 5.6 months) and had a different toxicity profile, with more cases of anemia and thrombocytopenia, while PacCBev was associated with higher rates of neutropenia and alopecia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. Patel, JD., Socinski, MA., Garon, EB., et al.[2022]

The combination of carboplatin, pemetrexed, and bevacizumab showed a response rate of 52% in 27 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), indicating its efficacy in treating this condition.

The treatment was generally well-tolerated, with no severe grade 4 or 5 toxicities reported, although some patients experienced manageable side effects like anemia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin/pemetrexed/bevacizumab in the treatment of patients with advanced non-small-cell lung cancer: a single-institution experience. Malhotra, B., Evans, T., Weiss, J., et al.[2022]

The combination of pemetrexed and carboplatin as first-line chemotherapy for malignant pleural mesothelioma showed a moderate overall response rate of 25% among 76 patients, with 21% achieving partial responses and 4% complete responses.

While the treatment was associated with some toxicity, with 47.3% of patients experiencing grade 3 hematological toxicity, the overall safety profile was considered acceptable, and the median survival for patients was estimated at 14 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Castagneto, B., Botta, M., Aitini, E., et al.[2020]

In a study involving 361 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed and carboplatin (Pem+Cb) did not show a significant advantage in progression-free survival without grade 4 toxicity compared to paclitaxel, carboplatin, and bevacizumab (Pac+Cb+Bev).

While both treatment regimens were generally well tolerated, Pem+Cb was associated with higher rates of grade 3/4 anemia and thrombocytopenia, whereas Pac+Cb+Bev had more cases of grade 3/4 neutropenia and alopecia, indicating differing toxicity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. Zinner, RG., Obasaju, CK., Spigel, DR., et al.[2022]

In a multicenter phase II trial involving 129 patients with bronchogenic carcinoma, carboplatin showed an overall response rate of 17.8%, with a notably higher response rate of 28.4% in patients with small-cell lung cancer.

The treatment was associated with significant toxic effects, particularly thrombocytopenia and leukopenia, affecting nearly half of the patients, but it did not result in renal, aural, or neurotoxicities, indicating a relatively safe profile compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carboplatin in patients with nonresected lung cancer. Japan Cooperative Oncology Group on Lung Cancer. [2019]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

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). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

A phase I trial involving 33 patients tested the combination of cisplatin and carboplatin, revealing that while the combination is feasible, it can lead to unexpectedly severe thrombocytopenia (low platelet count) when using specific doses, particularly 280 mg/m2 carboplatin with 25 mg/m2 cisplatin.

Despite the risk of thrombocytopenia, the combination therapy showed promising responses in tumors known to be responsive to platinum-based treatments, suggesting that further investigation into this combination is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum analogue combination chemotherapy: cisplatin and carboplatin--a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. Trump, DL., Grem, JL., Tutsch, KD., et al.[2017]

In a study of 70 patients with inoperable non-small cell lung cancer (NSCLC), carboplatin alone showed a 16% overall response rate with an acceptable safety profile, indicating its potential as a treatment option.

Combination therapies involving carboplatin with other drugs like etoposide and vinblastine yielded response rates of 11%, 12%, and 20%, respectively, but with increased toxicity, particularly myelosuppression, highlighting the need to balance efficacy and safety in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience. Green, MR., Kreisman, H., Doll, DC., et al.[2018]

In a study of 70 elderly patients (aged 70 and over) with advanced non-small cell lung cancer, both pemetrexed combined with carboplatin and gemcitabine combined with carboplatin showed similar efficacy, with response rates of 28.6% and 22.9%, respectively.

However, the pemetrexed plus carboplatin regimen had significantly lower rates of severe toxicities, such as neutropenia and nausea, making it a safer option for elderly patients undergoing treatment for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer]. Shi, X., Yu, XM., Zhang, YP., et al.[2022]

The combination of docetaxel and cisplatin showed a response rate of 32% and a median survival of 11.5 months in patients with advanced non-small-cell lung cancer (NSCLC), indicating its efficacy as a treatment option.

When combined with carboplatin, docetaxel demonstrated an improved response rate of 36% and a longer median survival of 13.9 months, suggesting that this combination may have a better safety profile and therapeutic index compared to the cisplatin combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in combination with platinum compounds for non small-cell lung cancer. Belani, CP.[2019]

Carboplatin alone demonstrated a 20% response rate in previously untreated patients with advanced non-small cell lung cancer (NSCLC), indicating its effectiveness as a single-agent treatment.

The combination of carboplatin and etoposide showed a higher response rate of 26.7%, but it also resulted in significantly greater myelosuppressive toxicity, suggesting that while the combination is effective, it may come with increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II studies with carboplatin in non-small cell lung cancer. Gatzemeier, U., Heckmayr, M., Neuhauss, R., et al.[2018]

In a phase II trial involving 37 patients with advanced non-small cell lung cancer, the combination of carboplatin and gemcitabine showed promising efficacy, with 8.1% achieving complete response and 24.3% achieving partial response after treatment.

The treatment was well-tolerated, with mild hematological toxicity, and a median survival of 10 months, suggesting that this regimen could be a viable palliative option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and gemcitabine in the palliative treatment of stage IV non-small cell lung cancer: definitive results of a phase II trial. Tassinari, D., Fochessati, F., Arcangeli, V., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. [2023]

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

PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. [2022]

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

Carboplatin/pemetrexed/bevacizumab in the treatment of patients with advanced non-small-cell lung cancer: a single-institution experience. [2022]

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

Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). [2020]

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

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. [2022]

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

Phase II study of carboplatin in patients with nonresected lung cancer. Japan Cooperative Oncology Group on Lung Cancer. [2019]

7. 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]

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

Platinum analogue combination chemotherapy: cisplatin and carboplatin--a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. [2017]

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

Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience. [2018]

10. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer]. [2022]

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

Docetaxel in combination with platinum compounds for non small-cell lung cancer. [2019]

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

Phase II studies with carboplatin in non-small cell lung cancer. [2018]

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

Carboplatin and gemcitabine in the palliative treatment of stage IV non-small cell lung cancer: definitive results of a phase II trial. [2022]