What is the mechanism of action of this treatment?

Pembrolizumab, a PD-1 inhibitor, blocks the PD-1 pathway to reactivate T-cells, enabling them to attack cancer cells. Olaparib, a PARP inhibitor, prevents cancer cells from repairing their DNA, leading to cell death. Combining these treatments can enhance anti-tumor responses by both boosting immune activity and directly causing cancer cell death, which is particularly beneficial for NSCLC patients.

What side effects are associated with this type of intervention?

Pembrolizumab, a PD-1 inhibitor, commonly causes immune-related adverse effects such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis, along with fatigue, rash, and pruritus. Olaparib, a PARP inhibitor, is associated with nausea, fatigue, anemia, and other hematologic toxicities. When combined with chemotherapy, these treatments can increase the risk of severe adverse effects, including neutropenia, febrile neutropenia, and gastrointestinal symptoms. While effective, these treatments carry significant risks of both immune-related and hematologic toxicities.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has received FDA approval for the treatment of Non-Small Cell Lung Cancer (NSCLC), particularly for tumors with PD-L1 expression. It has demonstrated significant improvements in overall survival and progression-free survival when used alone or in combination with chemotherapy. Other similar PD-1/PD-L1 inhibitors, such as nivolumab and atezolizumab, have also been approved for NSCLC treatment. While the combination of pembrolizumab with a PARP inhibitor like olaparib is currently under study, there are no prior FDA approvals for this specific combination in NSCLC.

What other types of research exist?

Promising novel alternatives to Pembrolizumab plus Olaparib for NSCLC patients include: 1) Sintilimab plus pemetrexed and platinum, which has shown promising efficacy in a phase 3 study for nonsquamous NSCLC. 2) Ramucirumab plus Pembrolizumab, which has demonstrated improved overall survival in patients with progressive disease after initial immunotherapy. 3) Cabozantinib, with or without Atezolizumab, which has shown preliminary activity in advanced NSCLC previously treated with immunotherapy. Further data from ongoing phase III trials are needed to confirm these findings.

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PD-1 Inhibitor

Pembrolizumab + Olaparib/Pemetrexed for Non-Small Cell Lung Cancer

Phase 3

Waitlist Available

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have not received prior systemic treatment for their advanced/metastatic NSCLC

Have stage IV nonsquamous NSCLC

Must not have

Has an active autoimmune disease that has required systemic treatment in past 2 years

Has predominantly squamous cell histology NSCLC

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is comparing two treatment combinations for a specific type of lung cancer. It aims to find out which combination helps patients live longer and keeps their cancer from getting worse. The treatments work by boosting the immune system, making it harder for cancer cells to repair themselves, or stopping their growth.

Who is the study for?

This trial is for adults with stage IV nonsquamous NSCLC who haven't had prior treatments. They must have a life expectancy of at least 3 months, be able to use contraception, and not be pregnant. Participants need good organ function and no severe allergies to the drugs being tested or their ingredients.

What is being tested?

The study compares two treatments: pembrolizumab combined with olaparib versus pembrolizumab with pemetrexed after initial therapy. It aims to see which combination is better for extending patients' lives without cancer progression and overall survival.

What are the potential side effects?

Possible side effects include allergic reactions, fatigue, nausea, blood cell count changes (which can increase infection risk), kidney or liver function issues, shortness of breath, and potential infertility due to treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I haven't had systemic treatment for my advanced lung cancer.

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My lung cancer is advanced (stage IV) and not squamous.

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I have provided a biopsy sample of my tumor that has not been treated with radiation.

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My lung cancer is not squamous cell type.

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My cancer is not suitable for EGFR, ALK, or ROS1 treatments.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated for an autoimmune disease in the last 2 years.

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My lung cancer is mainly squamous cell type.

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I have been diagnosed with MDS/AML or my condition suggests I might have it.

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I have another cancer that has worsened in the last 3 years and needs treatment.

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I have been treated with drugs targeting PD-L1, PD-L2, or T-cell receptors.

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I haven't had palliative radiotherapy in the last week and have no side effects needing steroids.

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I have been treated with olaparib or another PARP inhibitor before.

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I have lung disease or needed steroids for lung inflammation.

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I have an immune system disorder or am on long-term steroids.

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I have cancer that has spread to my brain or spinal cord.

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I have a history of HIV, hepatitis B, or active hepatitis C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Survival (OS)

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

Secondary study objectives

Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score

Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score

Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score

+9 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Pembrolizumab + Pemetrexed + Platinum Therapy + OlaparibExperimental Treatment5 Interventions

For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m\^2 IV on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21-day cycle for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until progressive disease, physician decision or intolerable toxicity.

Group II: Pembrolizumab + Pemetrexed + Platinum Therapy + PemetrexedActive Control4 Interventions

For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m\^2 IV on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21 day-cycle for up to 31 cycles PLUS maintenance pemetrexed IV 500 mg/m\^2 on Day 1 of each 21-day cycle. In the Maintenance Phase, the participant continues to receive maintenance pemetrexed until progressive disease, physician decision or intolerable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Carboplatin

2014

Completed Phase 3

~6120

Pemetrexed

2014

Completed Phase 3

~5550

Pembrolizumab

2017

Completed Phase 3

~3130

Cisplatin

2013

Completed Phase 3

~3120

Olaparib

2007

Completed Phase 4

~2190

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Pembrolizumab, a PD-1 inhibitor, blocks the PD-1 pathway to reactivate T-cells, enabling them to attack cancer cells. Olaparib, a PARP inhibitor, prevents cancer cells from repairing their DNA, leading to cell death. Combining these treatments can enhance anti-tumor responses by both boosting immune activity and directly causing cancer cell death, which is particularly beneficial for NSCLC patients.

Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11).Chemotherapy in Combination With Immune Checkpoint Inhibitors for the First-Line Treatment of Patients With Advanced Non-small Cell Lung Cancer: A Systematic Review and Literature-Based Meta-Analysis.