Evaluating the Combination of MK-3475 and Sterotactic Body Radiotherapy in Patients With Metastatic Melanoma or NSCLC

NCT02407171 | Completed Phase 1 Results DMC

• 1 other identifier: 1411014879
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 2-part prospective trial examining the ability of Stereotactic Body Radiation Therapy (SBRT) to induce a response to MK-3475, a humanized antibody to PD-1, in patients who progress on this antibody. Patients with metastatic melanoma will be enrolled after they have progressed on anti-PD-1 therapy. Patients with metastatic NSCLC (previously untreated with anti-PD-1 or anti-PD-L1 therapy) will be enrolled and treated with MK-3475 until they exhibit progression of disease. At this point (when patients have demonstrated progression of disease) a single target lesion will be selected and treated with SBRT, and then MK-3475 will be restarted and continued until there is further progression of disease. The first phase of the study is a radiation dose escalation with a constant dose of MK-3475. The second part of the study includes expansion cohorts of NSCLC and melanoma patients.

Conditions

Melanoma; Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Phase 2, Overall Response

  Phase 2 primary endpoint is the overall response count of patients to post-SBRT MK-3475. Overall response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST). The following are counts of those that were assessed to have the following responses: Complete response (CR), Partial response (PR), Stable disease (SD), Progressive disease (PD), Not Evaluable.

  up to 12 months

• Phase 1, Dose-Limiting Toxicity

  Phase 1 primary endpoint will be the presence of a dose limiting toxicity. Maximum tolerated dose will be the highest dose at which there is not a dose limiting toxicity. This could be either 3000 cGy in 5 fractions or 3 fractions. Presented are counts of the maximum tolerated of participants per arm. Results are summarized by Lung or Non-Lung targets overall.

  up to 12 months

Study Arms (4)

Non Small Cell Lung Cancer, Phase I

EXPERIMENTAL

Dose escalation cohort for patients with Non Small Cell Lung Cancer (NSCLC). The starting dose will be 3000 cGy in 5 fractions; there will be one dose escalation cohort (3000 cGy in 3 fractions), and if necessary one dose de-escalation cohort (1000 cGy in a single fraction). If there is dose-limiting toxicity at the lowest cohort, that arm will be closed and SBRT to that site will be discontinued.

Drug: MK-3475; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Non-Lung, Phase I

EXPERIMENTAL

Dose escalation cohort for non lung cancer patients. The starting dose will be 3000 cGy in 5 fractions; there will be one dose escalation cohort (3000 cGy in 3 fractions), and if necessary one dose de-escalation cohort (1000 cGy in a single fraction). If there is dose-limiting toxicity at the lowest cohort, that arm will be closed and SBRT to that site will be discontinued.

Drug: MK-3475; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Melanoma Expansion Cohort

EXPERIMENTAL

Phase 2a expansion cohort for patients with melanoma. Patients will be treated at the maximum tolerated dose discovered in phase I.

Drug: MK-3475; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Non Small Cell Lung Cancer Expansion Cohort

EXPERIMENTAL

Phase 2a expansion cohort for patients with NSCLC. Patients will be treated at the maximum tolerated dose discovered in phase I.

Drug: MK-3475; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

MK-3475 DRUG

200 mg every 2 weeks by IV infusion

Melanoma Expansion Cohort; Non Small Cell Lung Cancer Expansion Cohort; Non Small Cell Lung Cancer, Phase I; Non-Lung, Phase I

Stereotactic Body Radiation Therapy (SBRT) RADIATION

The starting dose will be 3000 cGy in 5 fractions; there will be one dose escalation cohort (3000 cGy in 3 fractions), and if necessary one dose de-escalation cohort (1000 cGy in a single fraction).

Melanoma Expansion Cohort; Non Small Cell Lung Cancer Expansion Cohort; Non Small Cell Lung Cancer, Phase I; Non-Lung, Phase I

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Have metastatic melanoma or NSCLC, or locally advanced NSCLC not suitable for curative-intent local therapy.
• For melanoma patients and NSCLC patients treated with prior anti-PD-1 therapy, patients must have received prior PD-1 therapy and have progressed (irPD) by irRC.
• Have 2 or more measurable sites of disease as defined by either RECIST 1.1, or cutaneous lesions at least 1 cm in greatest dimension
• Have at least one site of disease that is considered potentially suitable for treatment with SBRT
• Have provided tissue from an archival or newly obtained tissue sample of a tumor lesion, sufficient for analysis of PD-L1 and other biomarkers. Patients who have had PD-L1 analysis previously performed at Merck can substitute earlier analysis results and are not required to submit additional tissue for PD-L1 testing. Expression of PD-L1 is NOT required for study entry.
• Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 28 days of protocol treatment.
• Table 1. Adequate Organ Function Laboratory Values (System/Laboratory Value)
• Hematological
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL
• Renal
• Measured or calculated creatinine\*\* clearance ≤1.5 X upper limit of normal (ULN)

You may not qualify if:

• Has had radiation therapy within 2 weeks of the first protocol treatment.
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 2 weeks of the first protocol treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks of the first protocol treatment. The use of low-dose steroids for management of chronic conditions is allowed.
• Non-small cell lung cancer patients enrolling to MK-3475 as first protocol therapy (no prior anti-PD-1 therapy): Has had a prior monoclonal antibody within 4 weeks prior to first protocol treatment 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 of the first protocol treatment 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: Patients who have had prior treatments with Tyrosine Kinase Inhibitors (e.g. Tarceva) require only a 72-hour washout period prior to starting protocol treatment.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has known active and untreated brain (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an example of an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Those with a history of hypothyroidism who are now stable on hormone replacement will not be excluded. Those with Sjorgen's syndrome will not be excluded from the study.
• Has a history of (non-infectious) pneumonitis that required steroids, current pneumonitis or evidence of interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Melanoma; Lung Neoplasms

Interventions

pembrolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Allison Campbell, MD/PhD: Assistant Professor of Clinical Therapeutic Radiology
• Organization: Yale School of Medicine

allison.campbell@yale.edu

(203) 863-3700

Study Officials

• Allison Campbell, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2015
• First Posted: April 2, 2015
• Study Start: April 1, 2015
• Primary Completion: February 19, 2019
• Study Completion: February 19, 2019
• Last Updated: October 31, 2023
• Results First Posted: October 31, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)