Metastatic Non-small Cell Lung Cancer, Metastatic Triple-negative Breast Cancer
Conditions
Brief summary
This is a Phase II trial to determine the efficacy and safety of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy used as a window of opportunity treatment before pembrolizumab in patients with metastatic triple negative breast cancer (TNBC) and metastatic non-small cell lung cancer (NSCLC). In situ oncolytic virus therapy will consist of adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus valacyclovir therapy.
Detailed description
This is a Phase II trial to determine the efficacy and safety of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy used as a window of opportunity treatment before pembrolizumab in patients with metastatic triple negative breast cancer (TNBC) and metastatic non-small cell lung cancer (NSCLC). In situ oncolytic virus therapy will consist of adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus valacyclovir. Male and female patients aged ≥ 18 years with histologically confirmed locally advanced or metastatic TNBC that has relapsed on or is refractory to 1 or more lines of standard of care therapy or histologically or cytologically confirmed metastatic NSCLC that is immunotherapy and chemotherapy naïve or previously treated with 1 cycle of platinum-containing chemotherapy are eligible to participate in the study. ADV/HSV-tk (5 x 1011 viral particles) in a 2-mL total volume will be injected intratumorally on Day 0 of the study. Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days. Valacyclovir treatment will be administered 24 hours after the gene vector injection from Day 1 to Day 15 of the study. SBRT of 30 gray (Gy; 6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16 of the study. Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 of the study and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. The primary endpoint will be the objective response rate of ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. RECIST 1.1 will be used to assess treatment response. Secondary endpoints will include a) clinical benefit rate; b) duration of response; c) overall survival and progression-free survival rates; d) toxicity (toxicity will be defined as any treatment-related death or any ≥ grade 3 toxicity excluding alopecia and constitutional symptoms as assessed by the NCI CTCAE v4.03); and e) antitumor activity of ADV/HSV-tk plus valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab.
Interventions
BIOLOGICALADV/HSV-tk
Replication-defective recombinant adenovirus vector
DRUGValacyclovir
Prodrug of the antiviral drug acyclovir
RADIATIONSBRT
Low-dose SBRT
DRUGPembrolizumab
Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
Sponsors
Merck Sharp & Dohme LLC
The Methodist Hospital Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent/assent for the trial. 2. Male or female aged ≥18 years on the day of informed consent signing. 3. Histologically confirmed locally advanced or metastatic TNBC that has relapsed on or is refractory to standard of care therapy OR histologically or cytologically confirmed metastatic NSCLC that is immunotherapy and chemotherapy naïve or previously treated with 1 cycle of platinum-containing chemotherapy. Epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutation-negative NSCLC patients and NSCLC patients with EGFR or ALK genomic tumor aberrations that have failed FDA-approved targeted therapy for these aberrations will be eligible for enrollment in the study. 4. Measurable disease based on RECIST 1.1, a target lesion of suitable diameter (at least 1 cm) for SBRT, and a non-target lesion (visceral metastatic lesion) at least 1 cm in diameter for abscopal effect evaluation. 5. Willing to provide biopsy tissues as required by the study. 6. Eastern Cooperative Oncology Group performance status of 0 or 1. 7. Adequate organ function as defined by the following laboratory values: * Absolute neutrophil count ≥1,500/µL (without granulocyte colony stimulating factor support within 14 days of assessment) * Platelets ≥100,000/µL * Hemoglobin ≥8 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment) * White blood cell count \>2,500/µL and \<15,000/µL * Lymphocyte count ≥500/µL * Serum creatinine \<2 X upper limit of normal (ULN) * Serum total bilirubin ≤1.0 X ULN (Subjects with known Gilbert's disease who have serum bilirubin level ≤3 X ULN may be enrolled) * Asparate transaminase and alanine transaminase ≤2.5 X ULN with normal alkaline phosphatase (≤5 X ULN for subjects with liver metastases) OR ≤1.5 X ULN in conjunction with alkaline phosphatase \>2.5 X ULN * Albumin \>2.5 mg/dL * International normalized ratio or prothrombin time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants * aPTT ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants 8. Life expectancy ≥ 6 months. 9. ≥ 4 weeks since any major surgery, completion of radiation therapy, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy). 10. Female subjects of childbearing potential should have a negative serum pregnancy (beta-human chorionic gonadotropin) within 7 days prior to receiving the first dose of the trial treatment and should not be lactating. 11. Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study therapy. 12. Male subjects of childbearing potential must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study therapy.
Exclusion criteria
1. Unwilling or unable to comply with the study protocol. 2. Subjects for who bone metastases are the only available non-target lesions for abscopal effect evaluation. 3. Subjects with tumors for which SBRT is not considered appropriate standard therapy. This includes subjects with target lesions less than 1 cm in diameter and those with large central lung lesions. 4. 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 trial treatment. 5. 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. 6. Known history of active tuberculosis (Bacillus Tuberculosis). 7. Known or suspected hypersensitivity to pembrolizumab or any of its excipients or any component of the proposed regimen (gene vector/valacyclovir). 8. Known gallbladder or bile duct disease (i.e., infection or cholecystitis) or acute or chronic pancreatitis. 9. Eastern Cooperative Oncology Group performance status of ≥2 or oxygen dependence (e.g., advanced chronic obstructive pulmonary disease). 10. Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications (valacyclovir). 11. Congestive heart failure: New York Association class III or IV heart failure or unstable angina. 12. Sustained or clinically significant cardiac arrhythmias including sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block (Mobitz II or higher atrioventricular nodal block), prolonged corrected QT interval (longer than 470 milliseconds), or history of acute myocardial infarction. 13. Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes or Parkinson's disease), human immunodeficiency virus (HIV), cirrhosis, uncontrolled hypothyroidism, or cardiac failure. 14. History of syncope or family history of idiopathic sudden death. 15. Targeted small molecule therapy or monoclonal antibody or radiation therapy within 3 weeks prior to study Day 0 or 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. 16. 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. 17. Known active central nervous system 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 4 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. 18. 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 19. History of (non-infectious) pneumonitis that required steroids or current pneumonitis. 20. Active infection requiring systemic therapy. 21. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 22. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 23. Pregnant or breastfeeding, expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through 120 days after the last dose of trial treatment, or is unwilling to practice an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to administration of trial treatment. 24. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (TNBC cohort only). 25. Prior treatment with immunomodulatory therapy or immunotherapy (TNBC cohort only). 26. Prior treatment with gene vector therapy. 27. Received prior systemic cytotoxic chemotherapy for metastatic disease (NSCLC cohort). 28. Known history of HIV (HIV 1/2 antibodies). 29. History of liver disease such as cirrhosis or known active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g., hepatitis C virus RNA \[qualitative\] is detected). 30. History of or current alcohol misuse/abuse within the past 12 months. 31. Major surgery within 4 weeks prior to study enrollment. 32. Received a live vaccine within 30 days of planned start of trial therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months). | The objective response rate (ORR) of ADV/HSV-tk plus (+) valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used to assess treatment response. Modified immune-related response criteria (irRC; derived from RECIST 1.1) will also be documented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months). | Duration of response to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab |
| Overall Survival Rate | After confirmed disease progression or starts a new therapy, the subject moves into the Survival Follow-up to be contacted every 12 weeks to assess for survival status until death, withdrawal, or end of study. Median duration of follow-up was 8.3 months. | Overall survival (OS) rate in subjects receiving ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab. OS is the time (measured in months) from intratumoral viral injection to death or last date of contact. |
| Number of Participants With Treatment-related Adverse Events | Adverse Events (AEs) and Serious Adverse Events (SAEs) will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab, (up to 24 months of treatment for patients without disease progression). | To document the toxicities associated with ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. Toxicity will be defined as the number of participants with any treatment-related death or any ≥ Grade 3 hematological toxicity excluding alopecia and constitutional symptoms, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03. |
| Clinical Benefit Rate | 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months). | Clinical benefit rate of ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab |
| Progression-free Survival in Months | 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. | To determine the progression-free survival (PFS) of ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC as measured in months and defined the number of months a patient remains free from disease progression. |
| Antitumor Activity | 30 days after the last dose of pembrolizumab | Measure the antitumor activity as assessed by RECIST 1.1. Modified immune-related response criteria will also be documented. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Computed Tomography-based Response of a Non-target Lesion | baseline and 30 days after the last dose of pembrolizumab | Measure the computed tomography-based response (RECIST 1.1) of a non-target lesion to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab |
| Change in Immunohistochemical Expression of Tumor-infiltrating Lymphocytes in Tumor Biopsy Tissues | baseline and 30 days after the last dose of pembrolizumab | Measure the change in immunohistochemical expression of tumor-infiltrating lymphocytes in tumor biopsy tissues in response to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab |
Countries
United States
Participant flow
Recruitment details
57 overall participants (28 TNBC and 29 NSCLS)
Pre-assignment details
The Triple Negative Breast Cancer (TNBC) patients with histologically confirmed locally advanced or metastatic TNBC that has relapsed or is refractory to ≥1 lines of standard of care therapy. The Non-Small Cell Lung Cancer (NSCLC) cohort will include male & female patients with confirmed metastatic NSCLC that is immunotherapy naïve or previously treated with a maximum of 1 immunotherapy regimen & chemotherapy naïve or previously treated with 1 cycle of platinum-containing chemotherapy.
Participants by arm
| Arm | Count |
|---|---|
| Single Arm ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | COVID-19 | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 40 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Categorical NSCLC <=18 years | 0 Participants |
| Age, Categorical NSCLC >=65 years | 20 Participants |
| Age, Categorical NSCLC Between 18 and 65 years | 8 Participants |
| Age, Categorical Overall <=18 years | 0 Participants |
| Age, Categorical Overall >=65 years | 24 Participants |
| Age, Categorical Overall Between 18 and 65 years | 32 Participants |
| Age, Categorical TNBC <=18 years | 0 Participants |
| Age, Categorical TNBC >=65 years | 4 Participants |
| Age, Categorical TNBC Between 18 and 65 years | 24 Participants |
| Ethnicity (NIH/OMB) NSCLC Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) NSCLC Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) NSCLC Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Overall Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Overall Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Overall Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) TNBC Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) TNBC Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) TNBC Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) NSCLC American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) NSCLC Asian | 1 Participants |
| Race (NIH/OMB) NSCLC Black or African American | 4 Participants |
| Race (NIH/OMB) NSCLC More than one race | 0 Participants |
| Race (NIH/OMB) NSCLC Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) NSCLC Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) NSCLC White | 23 Participants |
| Race (NIH/OMB) Overall American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Overall Asian | 6 Participants |
| Race (NIH/OMB) Overall Black or African American | 9 Participants |
| Race (NIH/OMB) Overall More than one race | 0 Participants |
| Race (NIH/OMB) Overall Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Overall Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Overall White | 41 Participants |
| Race (NIH/OMB) TNBC American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) TNBC Asian | 5 Participants |
| Race (NIH/OMB) TNBC Black or African American | 5 Participants |
| Race (NIH/OMB) TNBC More than one race | 0 Participants |
| Race (NIH/OMB) TNBC Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) TNBC Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) TNBC White | 18 Participants |
| Sex: Female, Male NSCLC Female | 12 Participants |
| Sex: Female, Male NSCLC Male | 16 Participants |
| Sex: Female, Male Overall Female | 40 Participants |
| Sex: Female, Male Overall Male | 16 Participants |
| Sex: Female, Male TNBC Female | 28 Participants |
| Sex: Female, Male TNBC Male | 0 Participants |
| TNBC and NSCLC patient distribution NSLC | 28 Participants |
| TNBC and NSCLC patient distribution TNBC | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 56 |
| other Total, other adverse events | 28 / 56 |
| serious Total, serious adverse events | 29 / 56 |
Outcome results
Primary
Objective Response Rate
The objective response rate (ORR) of ADV/HSV-tk plus (+) valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used to assess treatment response. Modified immune-related response criteria (irRC; derived from RECIST 1.1) will also be documented.
Time frame: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).
Population: A total of 56 patient's data was analyzed, 28 patients with mTNBC and 28 patients with NSCLC.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Single Arm | Objective Response Rate | Overall | Complete Response | 4 Participants |
| Single Arm | Objective Response Rate | Overall | Stable Diseases | 13 Participants |
| Single Arm | Objective Response Rate | Overall | Progressive Disease | 32 Participants |
| Single Arm | Objective Response Rate | Overall | Partial Response | 7 Participants |
| Single Arm | Objective Response Rate | TNBC | Complete Response | 2 Participants |
| Single Arm | Objective Response Rate | TNBC | Partial Response | 1 Participants |
| Single Arm | Objective Response Rate | TNBC | Stable Diseases | 3 Participants |
| Single Arm | Objective Response Rate | TNBC | Progressive Disease | 22 Participants |
| Single Arm | Objective Response Rate | NSCLC | Complete Response | 2 Participants |
| Single Arm | Objective Response Rate | NSCLC | Partial Response | 6 Participants |
| Single Arm | Objective Response Rate | NSCLC | Stable Diseases | 10 Participants |
| Single Arm | Objective Response Rate | NSCLC | Progressive Disease | 10 Participants |
Secondary
Antitumor Activity
Measure the antitumor activity as assessed by RECIST 1.1. Modified immune-related response criteria will also be documented.
Time frame: 30 days after the last dose of pembrolizumab
Population: At this point in the data analysis has not been completed, information will be updated as it becomes available.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Single Arm | Antitumor Activity | Overall | Partial Response | 7 Participants |
| Single Arm | Antitumor Activity | Overall | Stable Diseases | 13 Participants |
| Single Arm | Antitumor Activity | TNBC | Progressive Disease | 22 Participants |
| Single Arm | Antitumor Activity | NSCLS | Complete Response | 2 Participants |
| Single Arm | Antitumor Activity | NSCLS | Partial Response | 6 Participants |
| Single Arm | Antitumor Activity | NSCLS | Stable Diseases | 10 Participants |
| Single Arm | Antitumor Activity | NSCLS | Progressive Disease | 10 Participants |
| Single Arm | Antitumor Activity | Overall | Complete Response | 4 Participants |
| Single Arm | Antitumor Activity | Overall | Progressive Disease | 32 Participants |
| Single Arm | Antitumor Activity | TNBC | Complete Response | 2 Participants |
| Single Arm | Antitumor Activity | TNBC | Partial Response | 1 Participants |
| Single Arm | Antitumor Activity | TNBC | Stable Diseases | 3 Participants |
Secondary
Clinical Benefit Rate
Clinical benefit rate of ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab
Time frame: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).
Population: The Clinical Benefit Rate measured as Complete Response plus Partial Response plus Stable Disease
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | Clinical Benefit Rate | Overall | 24 Participants |
| Single Arm | Clinical Benefit Rate | NSCLC | 18 Participants |
| Single Arm | Clinical Benefit Rate | TNBC | 6 Participants |
Secondary
Duration of Response
Duration of response to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab
Time frame: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).
Population: Median duration of response from last line of treatment (range), months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Arm | Duration of Response | TNBC | 2 Months |
| Single Arm | Duration of Response | NSCLC | 5.5 Months |
Secondary
Number of Participants With Treatment-related Adverse Events
To document the toxicities associated with ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. Toxicity will be defined as the number of participants with any treatment-related death or any ≥ Grade 3 hematological toxicity excluding alopecia and constitutional symptoms, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03.
Time frame: Adverse Events (AEs) and Serious Adverse Events (SAEs) will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab, (up to 24 months of treatment for patients without disease progression).
Population: The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | Number of Participants With Treatment-related Adverse Events | Total with Related SAE | 2 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events | TNBC | 2 Participants |
| Single Arm | Number of Participants With Treatment-related Adverse Events | NSCLC | 0 Participants |
Secondary
Overall Survival Rate
Overall survival (OS) rate in subjects receiving ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab. OS is the time (measured in months) from intratumoral viral injection to death or last date of contact.
Time frame: After confirmed disease progression or starts a new therapy, the subject moves into the Survival Follow-up to be contacted every 12 weeks to assess for survival status until death, withdrawal, or end of study. Median duration of follow-up was 8.3 months.
Population: Median overall survival for all patient and for patients with clinical benefit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Arm | Overall Survival Rate | TNBC | 6.6 Months |
| Single Arm | Overall Survival Rate | NSCLC | 12.9 Months |
Secondary
Progression-free Survival in Months
To determine the progression-free survival (PFS) of ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC as measured in months and defined the number of months a patient remains free from disease progression.
Time frame: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up.
Population: Median duration of progression free response from last line of treatment (range), months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Arm | Progression-free Survival in Months | TNBC | 2.5298 months |
| Single Arm | Progression-free Survival in Months | NSCLC | 7.4 months |
Other Pre-specified
Change in Immunohistochemical Expression of Tumor-infiltrating Lymphocytes in Tumor Biopsy Tissues
Measure the change in immunohistochemical expression of tumor-infiltrating lymphocytes in tumor biopsy tissues in response to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab
Time frame: baseline and 30 days after the last dose of pembrolizumab
Other Pre-specified
Computed Tomography-based Response of a Non-target Lesion
Measure the computed tomography-based response (RECIST 1.1) of a non-target lesion to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab
Time frame: baseline and 30 days after the last dose of pembrolizumab