Rucaparib + Pembrolizumab for Lung Cancer

Not currently recruiting at 3 trial locations

Overseen By Cancer AnswerLine

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Corticosteroids, PARP inhibitors

Disqualifiers: CNS metastases, Autoimmune disease, Active infection, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 24

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments, rucaparib and pembrolizumab (an immunotherapy drug), to determine their safety and effectiveness for people with stage IV non-squamous non-small cell lung cancer (NSCLC) whose cancer has not progressed after initial therapy. The goal is to assess whether these drugs can prevent the cancer from worsening post-treatment. The trial seeks participants diagnosed with this specific type of lung cancer who lack certain genetic mutations in their tumors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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, if you are on daily corticosteroids greater than 10mg of prednisone (or its equivalent), you would be excluded from the study.

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

Research has shown that combining rucaparib and pembrolizumab may help treat lung cancer. In one study, 14 patients received this treatment combination. Some patients experienced partial tumor shrinkage, while others saw their cancer stop growing. These results suggest the treatment might help control the cancer.

Regarding safety, these treatments are generally well-tolerated. Some patients might experience side effects, but serious issues are uncommon. Both rucaparib and pembrolizumab have been used for other conditions, providing some confidence in their safety. However, discussing potential risks with a doctor before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Rucaparib and Pembrolizumab for lung cancer because it offers a unique approach compared to current treatments. While most standard treatments rely on chemotherapy and targeted therapies, this combination harnesses the power of immunotherapy with Pembrolizumab, which helps the immune system recognize and attack cancer cells. Rucaparib adds another layer by inhibiting specific enzymes that cancer cells use to repair their DNA, potentially increasing their vulnerability to immune attack. This dual approach aims to enhance treatment effectiveness and offer new hope for patients who may not respond to existing therapies.

What evidence suggests that the combination of Rucaparib and Pembrolizumab might be an effective treatment for lung cancer?

Research has shown that combining rucaparib and pembrolizumab may help treat non-small cell lung cancer (NSCLC). In this trial, all participants will receive induction therapy with pembrolizumab, pemetrexed, and carboplatin, followed by maintenance therapy with pembrolizumab and rucaparib. One study found that patients who received this combination experienced tumor shrinkage, and in some cases, the cancer stopped growing. Early results suggest this combination might help control the disease after initial treatment. Pembrolizumab is already used to treat certain lung cancers by boosting the immune system to fight cancer cells. While more information is needed, these findings offer hope for patients with advanced NSCLC. ^{1 2 3 4 5}

Who Is on the Research Team?

Angel Qin

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage IV non-squamous NSCLC who've had no disease progression after initial treatment. They must be able to use contraception, have good organ function and performance status, and a life expectancy over 3 months. Excluded are those with prior PD-1/PD-L1 therapy, active autoimmune diseases or infections, certain psychiatric disorders, pregnancy/breastfeeding intentions within the study period.

Inclusion Criteria

My organs are functioning well.

I will use effective birth control during and for 6 months after the study.

My lung cancer is advanced, without certain genetic changes, and can be measured.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I had cancer before, but it's been treated and hasn't come back in over 5 years.

I take more than 10mg of prednisone or equivalent daily for another condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive induction therapy with Pembrolizumab, Pemetrexed, and Carboplatin

9 weeks

3 visits (in-person, every 21 days)

Maintenance Therapy

Participants receive maintenance therapy with Pembrolizumab and Rucaparib

Up to 5 years

Visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Rucaparib

Trial Overview The trial tests oral rucaparib combined with intravenous pembrolizumab as maintenance therapy post-induction with carboplatin/pemetrexed/pembrolizumab in patients without progressive disease. It's a single-arm Phase I/II study evaluating safety and effectiveness of this combination.

How Is the Trial Designed?

Group I: Rucaparib and Pembrolizumab Maintenance Experimental Treatment 4 Interventions

All patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m\^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days). This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle).

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

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

Clovis Oncology, Inc.

Industry Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

Published Research Related to This Trial

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]

In the phase II KEYNOTE-199 study involving 258 patients with metastatic castration-resistant prostate cancer (mCRPC), pembrolizumab demonstrated modest antitumor activity, with objective response rates of 5% in PD-L1-positive patients and 3% in PD-L1-negative patients, indicating some effectiveness in this challenging population.

The treatment was generally well-tolerated, with 60% of patients experiencing treatment-related adverse events, but only 5% discontinuing due to these events, suggesting that pembrolizumab has an acceptable safety profile while providing encouraging overall survival estimates, particularly in patients with bone-predominant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Antonarakis, ES., Piulats, JM., Gross-Goupil, M., et al.[2021]

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, 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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a real-life study of 108 patients with advanced non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score of ≥50%, pembrolizumab showed a median progression-free survival of 10.1 months, similar to results from the KEYNOTE-024 trial.

The treatment was generally well-tolerated, with only 8% of patients experiencing grade 3 adverse events, and no severe (grade 4 or 5) adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. Amrane, K., Geier, M., Corre, R., et al.[2021]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

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]

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

Citations

1. jto.org jto.org/article/S1556-0864(23)01356-4/fulltext

P2.06-08 Phase I/II Study of Rucaparib and ... Here we report the early results of the 14 patients who received at least one cycle of maintenance rucaparib and pembrolizumab. The median age was 59 and 64% ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11539152/

Update on Combination Strategies of PARP Inhibitors - PMC Results from the study indicated that a partial response was observed in three patients, while stable disease was maintained in seven patients.

3. jto.org jto.org/article/S1556-0864(23)01356-4/pdf

P2.06-08 Phase I/II Study of Rucaparib and ... standard treatment in advanced non-small cell lung cancer (NSCLC). CTONG1901 was to compare efficacy and safety of sintilimab and pembrolizumab, in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8423634/

Efficacy and safety of anti-PD-1-based therapy in ... As of March 18, 2020, all patients were evaluable, and 35 (87.5%) PFS events and 27 (67.5%) deaths had occurred. The integrate ORR was 27.5%, with a median ...

5. merck.com merck.com/news/merck-announces-keylynk-008-trial-evaluating-keytruda-pembrolizumab-plus-lynparza-olaparib-for-patients-with-metastatic-squamous-non-small-cell-lung-cancer-to-stop-for-futility/

Merck Announces KEYLYNK-008 Trial Evaluating ... At the interim analysis 3, KEYTRUDA in combination with chemotherapy followed by KEYTRUDA plus LYNPARZA did not demonstrate an improvement in ...