UCDCC#272: IL-2, Radiotherapy, and Pembrolizumab in Patients Refractory to Checkpoint Blockade

NCT03474497 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: 1166212
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase I/II study that will evaluate the safety and toxicity of this combinatorial approach. Eligible patients \>18 years of age with histologically proven metastatic NSCLC, melanoma, RCC, or HNSCC who have failed PD-1 / PD-L1 checkpoint blockade therapy will be enrolled. Patients must have a candidate treatment lesion (subcutaneous, nodal, or visceral) accessible and safe for radiotherapy and serial intralesional injections as specified by the protocol. They must also have at least one target lesion (distinct from treatment lesion and outside of treatment lesion radiation field) evaluable for response by RECIST. This study will consist of a phase I dose escalation using a standard 3+3 design to determine safety and MTD of intralesional IL-2 which will be dose escalated in conjunction with standard fixed doses of RT and Pembrolizumab. At the MTD there will be a phase II dose expansion which will incorporate a simon-two stage design to assess efficacy and safety. Patients will receive pembrolizumab and intralesional IL-2 in combination with hypofractionated radiotherapy.

Conditions

Non Small Cell Lung Cancer; Metastatic Melanoma; Metastatic Renal Cell Carcinoma; Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (4)

• Abscopal Response Rate (ARR)

  To determine the abscopal response rate (ARR) defined as objective response rate (the number of patient that achieve a partial or complete response) at unirradiated sites using irRECIST criteria using imaging obtained every 60 days.

  Up to time of response, about 8.5 months.

• Overall Response Rate (ORR)

  Overall response rate (ORR) defined as the number of patients that achieve partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions

  Up to time of response, about 8.5 months.

• Disease Control Rate (DCR)

  Disease control rate (DCR) defined as the number of patients whose best overall response is either complete response (CR), partial response (PR) or stable disease (SD), as assessed by Response Evaluation Criteria in Solid Tumors Criteria version 1.1 (RECIST v1.1) for target lesions.

  Up to about 10 months.

• Progression Free Survival (PFS)

  Progression free survival (PFS) defined as the median time from initiation of study intervention to progressive disease, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Up to about 7.3 months.

Secondary Outcomes (2)

• Maximum Tolerated Dose (MTD) (Phase 1)

  Up to 90 days of treatment

• Safety Profile and Toxicity

  Up to about 5.5 years

Study Arms (1)

Pembrolizumab/IL-2/Radiotherapy

EXPERIMENTAL

All patients will receive pembrolizumab and intralesional IL-2 in combination with hypofractionated radiotherapy.

Drug: IL-2; Drug: Pembrolizumab; Radiation: Radiotherapy

Interventions

IL-2 DRUG

• A total of four interleukin-2 treatments will be delivered into the treatment lesion by intralesional injection biweekly (at least 48 hours apart) starting 24-96 hours after the completion of radiotherapy and to be completed during the second on-trial cycle of Pembrolizumab. Intralesional injections will be performed by direct visualization and/or palpation of the lesion or under ultrasound or CT guidance as indicated.

Pembrolizumab/IL-2/Radiotherapy

Pembrolizumab DRUG

Pembrolizumab will be delivered at 200 mg in three week cycles per standard protocol.

Pembrolizumab/IL-2/Radiotherapy

Radiotherapy RADIATION

Radiotherapy will be delivered to the treatment lesion during the second cycle of therapy using an 8 Gy x 3 fractions palliative regimen. Fractions may be delivered on consecutive or every other day but must be completed during week 1-2 of cycle 2 and will not be repeated in future cycles.

Also known as: Radiation Therapy

Pembrolizumab/IL-2/Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years of age with histologically proven metastatic NSCLC, melanoma, RCC, or head and neck SCC.
• Failure to respond to checkpoint blockade therapy or previously responding patients who progress on PD-1/PD-L1 checkpoint blockade therapy.
• ECOG (Eastern Cooperative Oncology Group) performance status score of 0 - 1 (Appendix 1)
• Presence of a candidate treatment lesion (subcutaneous or nodal lesions are preferable but visceral lesions will be considered) accessible and safe for radiotherapy and serial intralesional injections.
• Presence of at least one target lesion (distinct from treatment lesion and outside of treatment lesion radiation field) evaluable for response by irRECIST
• Life expectancy ≥ 6 months
• Demonstrate adequate organ function as defined in Table 2, all screening labs should be performed within 10 days of treatment initiation.
• (Note: see protocol for table 2)
• No other active malignancy.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Signed informed consent.

You may not qualify if:

• Uncontrolled concomitant disease.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Use of inhaled or topical steroids or systemic corticosteroids \< 10 mg/ day is permitted.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) (excluding PD-1/PD-L1 inhibitor) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History of severe autoimmune disease.
• Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrollment (with the exception of checkpoint blockade therapy).
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications within past 4 weeks or 5 half-lives whichever is shorter. Use of inhaled or topical steroids or systemic corticosteroids \< 10 mg/ day is permitted.

Sponsors & Collaborators

• Megan Daly, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California Davis Medical Center

Sacramento, California, 97817, United States

Location

Related Links

• Learn more or sign up for the study here!

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Carcinoma, Renal Cell; Squamous Cell Carcinoma of Head and Neck

Interventions

Interleukin-2; pembrolizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Therapeutics

Results Point of Contact

• Title: Leslie Garcia
• Organization: University of California, Davis

lesgarcia@ucdavis.edu

916-734-60156

Study Officials

• Megan Daly, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: All patients will receive pembrolizumab and intralesional IL-2 in combination with hypofractionated radiotherapy.

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: March 22, 2018
• Study Start: May 20, 2019
• Primary Completion: April 22, 2025
• Study Completion: February 1, 2026
• Last Updated: January 29, 2026
• Results First Posted: January 29, 2026

Record last verified: 2025-11

Locations

US (2)