Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors

Study Overview
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Brief Summary
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Based on the overwhelming positive response to this survey and the large number of patients being treated with PD-1/PD-L1 therapy in the UPMC system, the investigators are proposing a trial that will randomize patients who have disease stability to stop treatment at 1 year or continue treatment until disease progression. The investigators anticipate that the results of this study will answer questions regarding the optimal duration of treatment. therapy.

Detailed Description
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Within the UPMC system, approximately 2,300 patients received PD-1/PD-L1 therapy for a variety of advanced solid tumors within the past year. It is anticipated that this number will increase as the clinical indications for treatment with these agents also increase. The investigators conducted a survey of 60 Medical Oncologists within the UPMC system regarding their interest in a trial that will attempt to address the question of optimal length of PD-1/PD-L1 treatment. Fifty-two (86.7%) physicians indicated that they would participate in a clinical trial that had a primary goal of determining whether it was feasible to stop immunotherapy after 1 year of treatment.

Official Title
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Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors

Conditions
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Advanced Solid Tumors, NSCLC, Bladder Cancer, HNSCC, Renal Cancer, Melanoma, Anal Cancer, Colorectal Cancer, Cholangiocarcinoma, Gastric Cancer, Hepatocellular Carcinoma, Merkel Cell Carcinoma, Cervical Cancer

Intervention / Treatment
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* Drug: Continue PD-1/PD-L1 Inhibitors treatment
* Other: Discontinue PD-1/PD-L1-1 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have an advanced solid tumor malignancy (specifically NSCLC, bladder, HNSCC, renal, melanoma, cervical, Merkel cell, MMR/MSI [colon, rectal, cholangio, esophageal, ovarian, uterine], anal, gastric and GE junction, hepatocellular, triple negative breast cancer) that is being treated with a PD-1/PD-L1 inhibitor including pembrolizumab, nivolumab, atezolizumab, durvalumab, or avelumab according to standard of care treatment. Patients who initially started treatment with another agent in combination with the PD-1/PD-L1 inhibitor, i.e. chemotherapy, ipilumumab, are eligible. Patients must have at least stable disease as evidenced by scans performed within 6 weeks of randomization. Signed Informed consent allowing randomization to stopping immunotherapy at 1 year ± 6 weeks versus continued treatment beyond 1 year. Patients can have measurable or non-measurable disease per iRECIST. Patients cannot be enrolled in a clinical trial. Exclusion Criteria: Patients with documented progressive disease prior to randomization. Patients with an immune-related toxicity preventing the continuation of treatment beyond 1 year at the treating physician's discretion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Continue Treatment with PD-1/PD-L1 inhibitor<br>Continued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment. | Drug: Continue PD-1/PD-L1 Inhibitors treatment<br>* Continued treatment with PD-1/PD-L1-1 inhibitor<br>* Other names: LIBTAYO (cemiplimab);|
| Experimental: Discontinue Treatment with PD-1/PD-L1-1 inhibitor<br>Discontinued standard of care treatment with PD-1/PD-L1 -1 checkpoint inhibitor after 12 months of checkpoint inhibitor treatment. | Other: Discontinue PD-1/PD-L1-1 inhibitor<br>* Discontinued treatment with PD-1/PD-L1-1 inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to next treatment | In patients who have already been treated with a PD-1 or PD-L1 inhibitor for one year, the difference in progression-free survival (time to next treatment, progression or death, whichever occurs first) between patients who stop treatment and patients who continue treatment. | Up to 36 months | 
| Progression-free Survival (PFS) (at between 2-3.9 months) | The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1.Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. | Between 2 months and 3.9 months | 
| Progression-free Survival (PFS) (at between 4-7.9 months) | The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1.Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. | Between 4 months and 7.9 months | 
| Progression-free Survival (PFS) | The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1.Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of irAEs (Immune-Related Adverse Events) | Proportion of participants in a disease stratum and treatment arm who experience at least one AE of any grade (per Common Terminology Criteria for Adverse Events (CTCAE v5.0)), at least possibly related to treatment in the categories of colitis, hepatitis, pnemonitis, hypophysitis or hypopituitarism, hypothyroidism, fatigue, diarrhea, rash, arthritis, arthralgia, back pain, musculoskeletal pain or myalgia, or any other category that is felt to be related to treatment. | Up to 36 months | 
| Overall Survival (OS) | The length of time from the start of treatment that patients are still alive. | Up to 36 months | 
| Best Objective Response (BOR) | Proportions of participants who restart for disease progression in each disease stratum, who experience a best objective response (progressive disease, stable disease, partial response, complete response) per RECIST v1.1 (Response Evaluation Criteria in Solid Tumors);Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm;Partial Response (PR): ≥ 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters;Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, (reference smallest sum diameters);Progressive Disease (PD): ≥ 20% increase in the sum of diameters of target lesions (reference smallest sum diameters); the sum must also demonstrate an absolute increase of at least 5 mm; (appearance ≥ 1 new lesions is considered progression). | Up to 36 months |