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RecruitingNCT07223424PSI-ImmuneUpdated Apr 16, 2026

Patient Preference for Subcutaneous vs. Intravenous Immune Therapy

A Phase 2 interventional study of nivolumab and pembrolizumab in Renal Cell Carcinoma, Non Small Cell Lung Cancer and Melanoma, sponsored by Diwakar Davar. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-16.

Sponsored by Diwakar Davar · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
880
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Renal Cell Carcinoma
  • Non Small Cell Lung Cancer
  • Melanoma
  • Colo-rectal Cancer (dMMR/MSI-H CRC)
  • Hepatocellular Carcinoma
  • Ulcerative Colitis
  • Esophageal Cancer
  • Squamous Cell Carcinoma
  • Gastric/GEJ
  • Cervical Cancer
  • Gastro-Esophageal Adenocarcinoma
  • Esophageal Adenocarcinoma
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Able to understand and willing to sign a written informed consent document.
  • Able to read and write in English.
  • 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.
  • Prior and concurrent therapy criteria

    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).

  • Locally advanced or advanced/metastatic solid tumor for which nivolumab OR pembrolizumab is on-label.

    • 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).
    • 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).
  • Cohort-specific criteria.

    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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).
    • 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.

Exclusion criteria

Exclusion Criteria:

  • Participant unable to receive nivolumab (or pembrolizumab) due to prior allergic reactions to nivolumab (or pembrolizumab) or any of its ingredients.
  • Has severe hypersensitivity (≥Grade 3) to nivolumab (or pembrolizumab) and/or any of its excipients.
  • Has had an allogenic tissue/solid organ transplant.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
880 participants (estimated)

Study arms

  • Active comparator
    Subcutaneous to IV

    SC nivolumab (or pembrolizumab) x3 cycles followed by IV nivolumab (or pembrolizumab) x3 cycles.

    Drug: nivolumab · Drug: pembrolizumab

  • Active comparator
    IV to Subcutaneous

    IV nivolumab (or pembrolizumab) x3 cycles followed by SC nivolumab (or pembrolizumab) x3 cycles

    Drug: nivolumab · Drug: pembrolizumab

Interventions

  • Drugnivolumab

    IV nivolumab (480mg Q4W), SC nivolumab (1200mg Q4W)

    Also known as: OPDIVO®

  • Drugpembrolizumab

    IV pembrolizumab (400mg Q6W) or SC pembrolizumab (790mg Q6W)

    Also known as: Keytruda®

05

What researchers measure

Primary outcomes

  1. Preference for Subcutaneous Nivolumab Treatment

    The proportion of patients with locally advanced or advanced/metastatic solid tumors who prefer SC to IV nivolumab.

    Time frame: Up to 48 months

  2. Preference for Subcutaneous Pembrolizumab Treatment

    The proportion of patients with locally advanced or advanced/metastatic solid tumors who prefer SC to IV pembrolizumab.

    Time frame: Up to 48 months

Secondary outcomes

  1. Therapy Administration Satisfaction Questionnaire

    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.

    Time frame: Up to 48 months

  2. Therapy Administration Satisfaction Questionnaire

    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.

    Time frame: Up to 48 months

  3. Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30

    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.

    Time frame: Screening Phase - Up to 28 days after signed consent

  4. Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30

    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.

    Time frame: At Day 1 of Treatment Cycle 3

  5. Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30

    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.

    Time frame: At Day 1 of Treatment Cycle 6

  6. Change in Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30

    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.

    Time frame: Up to 48 nmonths

  7. Health Related Quality of Life (HRQoL) - EQ-5D-5L

    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.

    Time frame: Screening Phase - Up to 28 days after signed consent

  8. Health Related Quality of Life (HRQoL) - EQ-5D-5L

    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.

    Time frame: At Day 1 of Treatment Cycle 3

  9. Health Related Quality of Life (HRQoL) - EQ-5D-5L

    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.

    Time frame: At Day 1 of Treatment Cycle 6

  10. Change Health Related Quality of Life (HRQoL) - EQ-5D-5L

    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.

    Time frame: Up to 48 months

  11. Physician-defined TTNT

    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.

    Time frame: Up to 48 months

  12. Incidence of irAEs

    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

    Time frame: Up to 48 months

06

Study locations

1 of 1 sites recruiting
  • UPMC Hillman Cancer Center
    Pittsburgh, Pennsylvania 15232, United States
    • Danielle L Bednarz, RN · Contact · bednarzdl@upmc.edu · 4126231191
    • Amy Rose, RN · Contact · kennaj@upmc.edu · 4126478587
    • Diwakar J Davar, MD · Principal investigator
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07223424
Lead sponsor
Diwakar Davar
Responsible party
Diwakar Davar (Associate Professor of Medicine, University of Pittsburgh) — Sponsor-investigator
First posted
Oct 31, 2025
Start date
Nov 4, 2025
Primary completion
Nov 30, 2030 (estimated)
Completion
Nov 30, 2030 (estimated)
Last update
Apr 16, 2026

Study contacts

Danielle L Bednarz, RN
Contact
bednarzdl@upmc.edu
4126231191
Amy Rose, RN
Contact
kennaj@upmc.edu
4126478587
Diwakar J Davar, MD
principal investigator · UPMC Hillman Cancer Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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