PD-1/PD-L1 Inhibitor Therapy Duration for Cancer

Overseen By Julie Urban, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Jason J. Luke, MD

Must be taking: PD-1/PD-L1 inhibitors

Disqualifiers: Progressive disease, Immune toxicity, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

578 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal duration for patients with certain advanced cancers to continue taking PD-1/PD-L1 inhibitors, a type of cancer treatment. Researchers are comparing two groups: one stops treatment after a year, while the other continues until cancer progression. The trial seeks to identify the best treatment duration. Patients with stable conditions such as lung, bladder, or breast cancer, who have been on these inhibitors for at least a year, may be suitable candidates for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering patients an opportunity to contribute to potentially groundbreaking advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. It focuses on patients already being treated with PD-1/PD-L1 inhibitors, so you may continue those treatments.

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

Research has shown that PD-1/PD-L1 inhibitors are usually well-tolerated by patients with advanced cancer, often causing fewer side effects than standard chemotherapy. However, some serious side effects can still occur. For instance, one study found that patients receiving anti-PD-1 therapy experienced more severe immune-related side effects than those on anti-PD-L1 therapy.

Overall, PD-1/PD-L1 inhibitors can be effective and safe, but awareness of potential risks is important. Patients should always discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatment that involves continuous administration of PD-1/PD-L1 inhibitors, this new approach is exploring the possibility of discontinuing the treatment after 12 months. Researchers are excited about this trial because it could potentially reduce side effects and healthcare costs by limiting the duration of treatment without compromising effectiveness. This trial aims to determine if a shorter treatment duration can still maintain cancer control, offering a promising alternative to the current long-term treatment options.

What evidence suggests that PD-1/PD-L1 inhibitor therapy is effective for cancer?

Research has shown that PD-1/PD-L1 inhibitors effectively treat various cancers, including melanoma, lung cancer, and gastrointestinal tumors. These treatments enhance the body's immune response against cancer cells. Studies have found that these inhibitors can prolong the time patients live without cancer progression and increase overall survival. In this trial, one group of participants will stop treatment with PD-1/PD-L1 inhibitors after 12 months, while another group will continue beyond 12 months. This approach aims to determine if adjusting the treatment duration improves outcomes. Overall, PD-1/PD-L1 inhibitors have proven effective and safe, with few side effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Dan Zandberg, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors (like lung, bladder, kidney cancer, etc.) who are responding to PD-1/PD-L1 inhibitors. They must have stable disease shown in scans within 6 weeks of joining and can't be on another clinical trial. Those with progressing disease or immune-related toxicity that stops treatment aren't eligible.

Inclusion Criteria

I am being treated with a PD-1/PD-L1 inhibitor for my advanced solid tumor cancer.

My latest scans show my disease hasn’t worsened in the past 6 weeks.

Patients can have either detectable or undetectable disease according to a specific set of guidelines.

Exclusion Criteria

My doctor stopped my immune therapy due to side effects.

You have shown signs that your disease is getting worse before starting the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PD-1/PD-L1 inhibitor treatment for 12 months

12 months

Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 36 months

Extension

Participants may continue or discontinue treatment based on randomization after 12 months

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• PD-1/PD-L1 Inhibitor

Trial Overview The study aims to find the best length of time for treating patients with PD-1/PD-L1 inhibitors. Participants will either stop treatment at one year or continue until their disease gets worse. The decision about which group a patient joins is made randomly.

How Is the Trial Designed?

Group I: Discontinue Treatment with PD-1/PD-L1-1 inhibitor Experimental Treatment 1 Intervention

Discontinued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment.

Group II: Continue Treatment with PD-1/PD-L1 inhibitor Active Control 1 Intervention

Continued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment.

Who Is Running the Clinical Trial?

Jason J. Luke, MD

Lead Sponsor

Trials

5

Recruited

720+

Dan Zandberg

Lead Sponsor

Trials

7

Recruited

330+

Antoinette J Wozniak

Lead Sponsor

Trials

1

Recruited

580+

Antoinette J Wozniak, MD

Lead Sponsor

Trials

1

Recruited

580+

Published Research Related to This Trial

In a study of 13 patients with various cancers who discontinued anti-PD(L)1 therapy after achieving stable disease, the median progression-free survival was 24.4 months, indicating that some patients can maintain disease control even after stopping treatment for a median of 12.6 months.

Upon retreatment after disease progression, 25% of patients achieved a partial response and 75% maintained stable disease, suggesting that resuming anti-PD(L)1 therapy can be effective and safe, as no severe adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of long-term responders to anti-programmed death 1 and anti-programmed death ligand 1 when being rechallenged with the same anti-programmed death 1 and anti-programmed death ligand 1 at progression. Bernard-Tessier, A., Baldini, C., Martin, P., et al.[2019]

In a study of 191 patients with non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors, those who experienced immune-related adverse events (irAEs) had significantly better treatment outcomes, with an objective response rate of 42.0% compared to 25.8% in those without irAEs.

The presence of irAEs was associated with improved progression-free survival, suggesting that these adverse events may indicate a more effective immune response to the treatment, although they did not correlate with overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events and Their Association With the Effectiveness of PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Real-World Study From China. Chen, X., Nie, J., Dai, L., et al.[2022]

In a study of 91 patients with advanced non-small cell lung cancer (NSCLC), the decision to continue or discontinue immune checkpoint inhibitor (ICI) treatment after 2 years was primarily influenced by the care center rather than clinical outcomes or tumor response.

After 2 years, progression-free survival rates were similar between those who continued ICI treatment (64.1%) and those who discontinued (68.5%), suggesting that the choice to continue treatment may not significantly affect long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pursuit or discontinuation of anti-PD1 after 2 years of treatment in long-term responder patients with non-small cell lung cancer. Ardin, C., Humez, S., Leroy, V., et al.[2023]

In a study of 38 patients with metastatic melanoma treated with a limited six-month PD-1 blockade program, the overall response rate was 39%, but only 33% of these responses were ongoing, indicating a shorter duration of response compared to other studies.

The median progression-free survival for patients who completed the six-month treatment was 12 months, suggesting that while the treatment is effective, limiting the duration may risk reducing the length of time patients benefit from the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited-duration anti-PD-1 therapy for patients with metastatic melanoma. Mäkelä, S., Kohtamäki, L., Laukka, M., et al.[2020]

In a meta-analysis of 27 randomized controlled trials involving 15,590 patients with advanced non-small cell lung cancer, treatment effect sizes for progression-free survival (PFS) and overall survival (OS) were found to be comparable, suggesting that PFS can be a reliable endpoint in clinical trials.

However, the analysis indicated that PFS may not be as reliable for trials using immunotherapy as a second-line treatment, highlighting the need for caution when interpreting PFS data without OS outcomes in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in treatment effect size between progression-free survival and overall survival in anti-PD-1/PD-L1 inhibitors-based trials in advanced NSCLC: a systematic review and meta-analysis. Zhou, Z., Ren, S., Chen, L., et al.[2022]

In a systematic review of 24 trials involving over 14,860 patients, PD-1/PD-L1 inhibitors significantly reduced the risk of death compared to conventional treatments, with a hazard ratio of 0.72, indicating a strong efficacy across various tumor types.

Patients with positive PD-L1 expression (≥1%) showed improved overall survival when treated with anti-PD-1/PD-L1 monotherapy, particularly in nonsmall cell lung cancer, suggesting that PD-L1 expression can be a useful biomarker for selecting patients for this type of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Value of PD-L1 Expression in Predicting the Efficacy of Anti-PD-1 or Anti-PD-L1 Therapy in Patients with Cancer: A Systematic Review and Meta-Analysis. Chen, XJ., Yuan, SQ., Duan, JL., et al.[2022]

In a study of 52 patients with metastatic melanoma who discontinued PD-1 therapy after 1 year, 75% remained without disease progression after a median follow-up of 20.5 months, suggesting that shorter treatment durations may be effective.

The findings indicate that elective discontinuation of PD-1 inhibitors at 1 year could potentially reduce treatment costs and side effects without compromising patient outcomes, as most patients maintained stable disease or responded positively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with elective discontinuation of PD-1 inhibitors at 1 year in patients with metastatic melanoma. Pokorny, R., McPherson, JP., Haaland, B., et al.[2023]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

In a systematic review of 125 clinical trials involving over 20,000 patients, 66% experienced at least one treatment-related adverse event from PD-1 and PD-L1 inhibitors, with fatigue, pruritus, and diarrhea being the most common.

Nivolumab was found to have a higher incidence of adverse events compared to pembrolizumab, and PD-1 inhibitors generally led to more severe adverse events than PD-L1 inhibitors, highlighting the importance of understanding these differences for clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis. Wang, Y., Zhou, S., Yang, F., et al.[2022]

In a study of 85 metastatic melanoma patients treated with anti-PD1 therapy, those with undetectable circulating tumor DNA (ctDNA) at baseline showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those with detectable ctDNA, indicating ctDNA levels can be a predictive biomarker for treatment outcomes.

Patients with high ctDNA levels (>500 copies/ml) at baseline or week 3 had poorer clinical outcomes, suggesting that monitoring ctDNA can provide valuable insights into tumor burden and response to therapy during anti-PD1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy. Seremet, T., Jansen, Y., Planken, S., et al.[2023]

In a study of 59 patients treated with PD-1 therapy for metastatic cancers, those whose treatment was stopped after 6 months due to response experienced a median immuno-oncology therapy-free survival of 12 months, indicating that shorter treatment durations can be effective.

The study also found that alternative response evaluation criteria were better than conventional methods in predicting therapy-free survival, suggesting that reevaluating how we assess treatment responses could improve patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early PD-1 Therapy Discontinuation in Responding Metastatic Cancer Patients. Iivanainen, S., Koivunen, JP.[2019]

In a meta-analysis of 18 studies involving 5,649 patients with non-small cell lung cancer, first-line therapy using PD-1/PD-L1 inhibitors showed a significantly higher risk of treatment-related adverse events (trAEs) and immune-related adverse events (irAEs) compared to subsequent therapies, indicating a need for careful monitoring in initial treatments.

Despite the higher incidence of adverse events in first-line therapy, the types of trAEs and irAEs were largely similar across different therapy lines, suggesting that while the severity may differ, the overall spectrum of side effects remains consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. Yang, Y., Pang, P., Xie, Z., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11915729/

Association of anti-PD-(L)1 treatment duration to efficacy in ... The results suggest that continuing the treatment over six months may not improve treatment outcomes. When matching our RWE on therapy efficacy ...

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-11833-6

Efficacy and safety of anti-PD-1 inhibitor versus ... - BMC Cancer Two-year ICI treatment was completed by 7.4% (5/68) and 8.1% (7/86) patients in the PD-1 and PD-L1 groups, respectively. Locoregional thoracic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5601788/

Effectiveness and safety of PD-1/PD-L1 inhibitors in the ... PD-1 inhibitors are more effective for improving the PFS, OS, and ORR of cancer patients with little toxicity, despite having little effect on increasing of the ...

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1616872/full

New dimensions of PD-1/PD-L1 inhibitor combination ... They have demonstrated remarkable efficacy in the treatment of various cancer types, including melanoma, lung cancer, and gastrointestinal tumors (7, 8).

5. jitc.bmj.com jitc.bmj.com/content/13/6/e011622

A real-world study on the efficacy and safety of low-dose ... Among patients receiving first-line monotherapy (n=25), mPFS was 34.6 months for low-dose (L), 59.8 months for standard-dose (S), and 17.4 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5388381/

Safety and Tolerability of PD‐1/PD‐L1 Inhibitors Compared ... Our analysis suggests that PD1/PD‐L1 inhibitors are better tolerated than standard‐of‐care chemotherapy in patients with advanced cancer. In addition to the ...

7. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-13129-1

Efficacy and safety of PD-1/PD-L1 inhibitors in patients with ... In a pooled analysis of four studies, selected based on available data, including 202 patients, the overall survival rate at 24 months was 65.05 ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666634025000960

Article Efficacy and safety of anti-PD-1 versus anti-PD-L1 in ... Anti-PD-1 therapy demonstrated better clinical outcomes and higher incidence of grade 3–5 immune-related adverse events to anti-PD-L1 in perioperative settings.

9. nature.com nature.com/articles/s41598-020-58674-4

Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for ... Thirty-three RCTs providing valid data for ORR revealed that cancer patients gained a significant ORR benefit from anti-PD-1/PD-L1 inhibitors ( ...

10. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1516735/full

A network comparison on efficacy and safety profiling of PD ... This study aims to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors, which have completed phase 3 clinical trials, as a first-line treatment in ...