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Under-the-Skin vs IV Nivolumab or Pembrolizumab: Patient Preference
This randomized crossover study asks whether adults with locally advanced or metastatic solid tumors prefer subcutaneous injections or intravenous infusions of nivolumab or pembrolizumab.
Registry title: Patient Preference for Subcutaneous vs. Intravenous Immune Therapy
1 recruiting U.S. site ↓Study at a glance
- Age
- 18 Years and older
- Treatment
- nivolumab or pembrolizumab
- Design
- Randomized
- Central study contact
- Danielle L Bednarz, RN4126231191bednarzdl@upmc.edu
- Sponsor
- Diwakar Davar
Research question
Do patients with eligible advanced solid tumors prefer receiving nivolumab or pembrolizumab by subcutaneous injection rather than intravenous infusion, and how do the approaches compare in satisfaction, quality of life, safety, and cancer-related outcomes?
Participant snapshot
Who the study is looking for
- The study is looking for adults age 18 or older with a locally advanced or advanced/metastatic solid tumor.
- The cancer must have an on-label use for nivolumab or pembrolizumab, and the investigator must determine that the person can receive that drug under standard care.
- The study includes people who have not started the planned study drug and people already receiving eligible immune-checkpoint therapy who may be willing to switch.
- Participants must be able to read and write in English and understand and sign written informed consent.
- The registry lists one recruiting location: UPMC Hillman Cancer Center in Pittsburgh, Pennsylvania.
Participation overview
What participation may involve
Participants receive nivolumab or pembrolizumab by both subcutaneous injection and intravenous infusion, with the order determined by random assignment, and report their preferences and experiences. What participation may involve: - Receive three treatment cycles by one administration method and then three cycles by the other method. - Complete questionnaires about treatment-administration satisfaction and which administration method is preferred. - Complete health-related quality-of-life questionnaires during screening and on day 1 of treatment cycles 3 and 6. - The study tracks time to the next therapy and immune-related adverse events that cause a dose hold or delay.
Study interventions
What participants may receive or do
- nivolumab: Nivolumab is given either intravenously at 480 mg every four weeks or by subcutaneous injection at 1,200 mg every four weeks. Participants cross from one administration method to the other.
- pembrolizumab: Pembrolizumab is given either intravenously at 400 mg every six weeks or by subcutaneous injection at 790 mg every six weeks. Participants cross from one administration method to the other.
Study design
How the comparison works
This is an open-label, randomized phase 2 crossover study. Each participant receives both subcutaneous and intravenous administration in an assigned order. Participants are randomly assigned to start with either subcutaneous treatment or intravenous treatment before crossing to the other method. The study has no masking, so participants and the study team know which administration method is being used. The two active-comparator groups differ by treatment order: three subcutaneous cycles followed by three intravenous cycles, or the reverse. The registry describes two active-comparator sequences and does not list a placebo arm.
Reported activities
Procedures and tests
- Therapy Administration Satisfaction Questionnaire for intravenous administration.
- Therapy Administration Satisfaction Questionnaire for subcutaneous administration.
- The 30-item EORTC QLQ-C30 questionnaire assesses functioning, symptoms, and overall health-related quality of life.
- The EQ-5D-5L questionnaire assesses mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.
- The study records immune-related adverse events that result in a dose hold or delay using Common Terminology Criteria for Adverse Events version 5.
- Screening must confirm that the participant can receive nivolumab or pembrolizumab under standard-care practices and meets the applicable cohort criteria.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Participants must be able to understand and willing to sign written informed consent.
- Participants must be able to read and write in English.
- An investigator must determine that the participant is eligible to receive nivolumab or pembrolizumab, alone or with an FDA-approved tyrosine kinase inhibitor or chemotherapy, under standard-care practices.
- Participants must have a locally advanced or advanced/metastatic solid tumor for which nivolumab or pembrolizumab is on-label.
- Cohorts A-1 and A-2 are for people whose planned nivolumab or pembrolizumab treatment, respectively, has not yet started.
- Cohorts B-1 and B-2 may include people already receiving the applicable study drug, or another immune-checkpoint inhibitor, who are willing to switch to an on-label nivolumab- or pembrolizumab-based treatment.
- People receiving nivolumab plus ipilimumab as induction may be considered for Cohort B-1 after induction, during planned maintenance, for applicable indications.
Possible reasons someone may not be able to join
- A person cannot participate if a prior allergic reaction to nivolumab, pembrolizumab, or one of their ingredients means they cannot receive the applicable drug.
- A history of severe, grade 3 or higher hypersensitivity to the applicable study drug or its inactive ingredients excludes participation.
- A prior allogeneic tissue or solid-organ transplant excludes participation.
- People for whom nivolumab plus ipilimumab is planned as maintenance are not eligible.
- People planning anti-PD-1 immunotherapy before surgery are not appropriate for enrollment at that time, although the registry says they may be considered when starting adjuvant therapy in an applicable cohort.
Important unknowns
What the record does not make clear
- The registry identifies some questionnaire time points but does not provide a complete visit schedule.
- The treatment sequence contains six cycles, but the registry does not state each participant's full participation or follow-up duration.
- The registry permits some FDA-approved chemotherapy or targeted-therapy combinations but does not specify every allowed regimen or whether it remains unchanged during crossover.
- The study is listed as recruiting, but the record does not identify which nivolumab or pembrolizumab cohorts are currently open.
- The record does not explain which treatment, research, or routine-care costs are covered or billed to insurance.
- The record does not state whether participants receive compensation.
- The record does not state whether transportation, parking, lodging, or other travel support is available.
- The record does not say whether questionnaires or follow-up activities can be completed remotely.
- The condition list names ulcerative colitis, while the eligibility criteria require an advanced solid tumor and use “UC” among cancer indications; the intended diagnosis is unclear from the record.
Before contacting the site
Questions for the study team
- Which nivolumab and pembrolizumab cohorts are currently open at UPMC Hillman Cancer Center?
- What is the complete visit schedule, and which activities occur outside routine cancer-treatment appointments?
- How long would participation and follow-up last for someone assigned to nivolumab versus pembrolizumab?
- Which chemotherapy or targeted-therapy combinations are permitted, and must those treatments remain unchanged during crossover?
- Which treatment and research costs are covered, and are compensation or travel support available?
- Does the condition entry for ulcerative colitis reflect an enrolling population, or is it a terminology error involving the abbreviation “UC”?
Before changing care
Questions for your gastroenterologist
- Would changing between subcutaneous and intravenous administration affect the continuity or monitoring of my current cancer treatment?
- Is my disease stable enough for a crossover study, and are there clinical concerns that the study's registry criteria do not address?
- What standard, approved treatment alternatives are available for my diagnosis if I do not pursue this study?
- How should my gastroenterology care and cancer treatment be coordinated if immune-related digestive symptoms occur?
- Could my gastrointestinal history or current medicines affect whether nivolumab or pembrolizumab is appropriate for me?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
The study will evaluate patient and Health Care Professional- reported preference for Subcutaneous (SC) compared with IV nivolumab administration or similarly for SC compared with IV pembrolizumab.
The development of SC nivolumab and SC pembrolizumab was intended to provide patients, physicians and health care systems compelling advantages to reduce the burden associated with ICI administration. However, despite the results of CheckMate 76K, Hillman Cancer Center utilization of SC nivolumab is poor. This study aims to formally assess, from the patients' perspective, whether SC administration of ICI agents is preferable to IV administration. Key secondary objectives include physician experience with SC vs. IV administration, cancer-related efficacy endpoints, and safety. Patients who are pending initiation of nivolumab monotherapy or nivolumab-based chemotherapy or targeted therapy combinations (Cohort A-1) will be enrolled. However, patients who are already receiving nivolumab or other ICI but are willing to be switched to nivolumab monotherapy or nivolumab-based combinations may be eligible to enroll in a separate cohort (Cohort B-1). US FDA has accepted a Biologics License Application from Merck for SC pembrolizumab for an FDA action date of 9/23/2025. Should SC pembrolizumab achieve FDA approval, we will aim to open 2 separate cohorts to evaluate patient preference for SC vs. IV pembrolizumab.
Study design and administration
- Organization
- University of Pittsburgh
- Organization class
- Other
- Organization study ID
- HCC 25-125
- Lead sponsor
- Diwakar Davar
- Sponsor class
- Other
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Crossover
- Primary purpose
- Treatment
- Masking
- None
- Who is masked
- Not provided
- Standard age groups
- Adult, Older Adult
Study arms
Active Comparator
Subcutaneous to IV
SC nivolumab (or pembrolizumab) x3 cycles followed by IV nivolumab (or pembrolizumab) x3 cycles.
Interventions: Drug: nivolumab, Drug: pembrolizumab
Active Comparator
IV to Subcutaneous
IV nivolumab (or pembrolizumab) x3 cycles followed by SC nivolumab (or pembrolizumab) x3 cycles
Interventions: Drug: nivolumab, Drug: pembrolizumab
Interventions
Drug
nivolumab
IV nivolumab (480mg Q4W), SC nivolumab (1200mg Q4W)
Drug
pembrolizumab
IV pembrolizumab (400mg Q6W) or SC pembrolizumab (790mg Q6W)
Eligibility
18 Years and older
All
Not accepted
Inclusion criteria (16)
- Able to understand and willing to sign a written informed consent document.Registry-derived · unreviewed
- Able to read and write in English.Registry-derived · unreviewed
- Must be eligible to receive nivolumab (Cohorts A-1, B-1) or pembrolizumab (Cohorts A-2, B-2) singly or in combination with other FDA-approved agents (TKIs or chemotherapy) according to standard of care practices, as determined by the clinical judgment of the investigator.Registry-derived · unreviewed
- Prior and concurrent therapy criteriaRegistry-derived · unreviewed
- o Patients should either be ICI-naïve (Cohorts A-1, A-2) or be currently receiving adjuvant or front-line PD-(L)1 based therapy singly or in combination with FDA-approved agents (TKIs or chemotherapy) (Cohorts B-1, B-2).Registry-derived · unreviewed
- Locally advanced or advanced/metastatic solid tumor for which nivolumab OR pembrolizumab is on-label.Registry-derived · unreviewed
- NOTE: IV nivolumab is FDA-approved in the following indications: RCC, melanoma, NSCLC, SCCHN, UC, dMMR/MSI-H CRC, HCC, esophageal cancer, and gastric, gastroesophageal and esophageal adenocarcinoma (gastric/GEJ).Registry-derived · unreviewed
- NOTE: IV pembrolizumab is FDA-approved in the following indications: RCC, melanoma, NSCLC, SCCHN, UC, dMMR/MSI-H CRC, HCC, esophageal cancer, gastric/GEJ, cervical cancer, cutaneous squamous cell carcinoma (cSCC), Merkel cell carcinoma (MCC), endometrial carcinoma, tumor mutational burden-high (TMB-H) cancers, triple negative breast cancer (TNBC).Registry-derived · unreviewed
- Cohort-specific criteria.Registry-derived · unreviewed
- Cohort A-1: Patients who are treatment-naive (i.e. for whom nivolumab is planned but has not yet been initiated) are eligible to enroll.Registry-derived · unreviewed
- Cohort B-1: Patients who are already receiving treatment with nivolumab (singly or in combination with TKI or chemotherapy) OR a different ICI-therapy but are willing to switch to nivolumab monotherapy or nivolumab based combinations may eligible to enroll if nivolumab is on-label for their cancer.Registry-derived · unreviewed
- Cohort A-2: Patients who are treatment-naive (i.e. for whom pembrolizumab is planned but has not yet been initiated) are eligible to enroll.Registry-derived · unreviewed
- Cohort B-2: Patients who are already receiving treatment with pembrolizumab (singly or in combination with TKI or chemotherapy) OR a different ICI-therapy but are willing to switch to pembrolizumab monotherapy or pembrolizumab based combinations may eligible to enroll if pembrolizumab is on-label for their cancer.Registry-derived · unreviewed
- NOTE: Patients who are currently receiving nivolumab + ipilimumab combination as induction may be eligible to enroll in Cohort B-1 following induction (i.e. during planned maintenance) in indications including but not limited to advanced/metastatic melanoma, ccRCC, MSI-H/dMMR mCRC.Registry-derived · unreviewed
- NOTE: Patients for whom nivolumab + ipilimumab combination is planned as maintenance are not eligible (i.e. NSCLC patients being treated per CheckMate-227 or CheckMate-9LA).Registry-derived · unreviewed
- NOTE: Patients for whom anti-PD-1 based immunotherapy is planned as neoadjuvant therapy are not appropriate. Such patients may be considered for enrollment at the time of commencing adjuvant therapy in cohorts A-2 or B-2 as appropriate.Registry-derived · unreviewed
Exclusion criteria (3)
- Participant unable to receive nivolumab (or pembrolizumab) due to prior allergic reactions to nivolumab (or pembrolizumab) or any of its ingredients.Registry-derived · unreviewed
- Has severe hypersensitivity (≥Grade 3) to nivolumab (or pembrolizumab) and/or any of its excipients.Registry-derived · unreviewed
- Has had an allogenic tissue/solid organ transplant.Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Preference for Subcutaneous Nivolumab Treatment
Time frame: Up to 48 months
The proportion of patients with locally advanced or advanced/metastatic solid tumors who prefer SC to IV nivolumab.
Primary outcome
Preference for Subcutaneous Pembrolizumab Treatment
Time frame: Up to 48 months
The proportion of patients with locally advanced or advanced/metastatic solid tumors who prefer SC to IV pembrolizumab.
Secondary outcome
Therapy Administration Satisfaction Questionnaire
Time frame: Up to 48 months
Patient assessed satisfaction with SC vs. IV nivolumab (or pembrolizumab) using Therapy Administration Satisfaction Questionnaire (using TASQ-IV) in patients with locally advanced or advanced/metastatic solid tumors pending initiation of nivolumab (or pembrolizumab) monotherapy or nivolumab- (or pembrolizumab-) based combinations.
Secondary outcome
Therapy Administration Satisfaction Questionnaire
Time frame: Up to 48 months
Patient assessed satisfaction with SC vs. IV nivolumab (or pembrolizumab) using Therapy Administration Satisfaction Questionnaire (using TASQ-SC) in patients with locally advanced or advanced/metastatic solid tumors pending initiation of nivolumab (or pembrolizumab) monotherapy or nivolumab- (or pembrolizumab-) based combinations.
Secondary outcome
Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30
Time frame: Screening Phase - Up to 28 days after signed consent
Patient reported HRQoL scores using the EORTC QLQ-C30 instrument. The categories/domains include functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), global health status and quality of life scale. Item scoring for functional items is 1 (Not at all) to 4 (Very much); Item scoring for global health items is 1 (Very poor) to 7 (Excellent). Total scores (all items) range from 0 to 100. For functional and global quality of life scales higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severe symptoms.
Secondary outcome
Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30
Time frame: At Day 1 of Treatment Cycle 3
Patient reported HRQoL scores using the EORTC QLQ-C30 instrument (30 items). The categories/domains include functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), and global health status and quality of life scale. Item scoring for functional and symptom items is 1 (Not at all) to 4 (Very much); Item scoring for global health items is 1 (Very poor) to 7 (Excellent). Total scores range from 0 to 100. For functional and global quality of life scales higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severe symptoms.
Secondary outcome
Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30
Time frame: At Day 1 of Treatment Cycle 6
Patient reported HRQoL scores using the EORTC QLQ-C30 instrument (30 items). The categories/domains include functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), and global health status and quality of life scale. Item scoring for functional and symptom items is 1 (Not at all) to 4 (Very much); Item scoring for global health items is 1 (Very poor) to 7 (Excellent). Total scores range from 0 to 100. For functional and global quality of life scales higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severe symptoms.
Secondary outcome
Change in Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30
Time frame: Up to 48 nmonths
Changes in patient reported HRQoL scores using the EORTC QLQ-C30 instrument. The categories/domains include functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), and global health status and quality of life scale. Item scoring for functional and symptom items is 1 (Not at all) to 4 (Very much); Item scoring for global health items is 1 (Very poor) to 7 (Excellent). Total scores range from 0 to 100. For functional and global quality of life scales higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severe symptoms.
Secondary outcome
Health Related Quality of Life (HRQoL) - EQ-5D-5L
Time frame: Screening Phase - Up to 28 days after signed consent
Patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.
Secondary outcome
Health Related Quality of Life (HRQoL) - EQ-5D-5L
Time frame: At Day 1 of Treatment Cycle 3
Patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.
Secondary outcome
Health Related Quality of Life (HRQoL) - EQ-5D-5L
Time frame: At Day 1 of Treatment Cycle 6
Patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.
Secondary outcome
Change Health Related Quality of Life (HRQoL) - EQ-5D-5L
Time frame: Up to 48 months
Change in patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.
Secondary outcome
Physician-defined TTNT
Time frame: Up to 48 months
Physician-defined time to next therapy (TTNT) is defined as the period from the start of the treatment to the start of the next line of treatment.
Secondary outcome
Incidence of irAEs
Time frame: Up to 48 months
Incidence of immune-related adverse events (irAEs) that result in a dose hold or delay in patients treated with either SC or IV nivolumab (or pembrolizumab) per Common Terminology Criteria for Adverse Events (CTCAE) guidelines v5
Recruiting locations in the United States
UPMC Hillman Cancer Center
RecruitingPittsburgh, Pennsylvania, 15232, United States
Danielle L Bednarz, RN4126231191bednarzdl@upmc.edu
Amy Rose, RN4126478587kennaj@upmc.edu
Diwakar J Davar, MD
Central study contacts
Registry dates
- First posted
- Oct 31, 2025
- Primary completion
- Nov 30, 2030
- Overall completion
- Nov 30, 2030
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.