Head and Neck Squamous Cell Carcinoma With Inoperable Recurrent or Progressive DiseasePhase 2NCT04685499
Phase 2 Study of OBP-301 (Telomelysin™) in Combination With Pembrolizumab and SBRT in Patients With HNSCC With Inoperable, Recurrent or Progressive Disease
A Phase 2 study testing OBP-301 and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma With Inoperable Recurrent or Progressive Disease, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
The purpose of this study is to test the effects, of the research study drug Telomelysin (OBP-301) in combination with pembrolizumab in subjects with inoperable, recurrent, or progressive squamous cell carcinoma of the head and neck. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma With Inoperable Recurrent or Progressive Disease
- What is being tested?
- OBP-301 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 3 May 2021to 3 Jun 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent/assent for the trial.
- Be >18 years of age on the day of signing the informed consent.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Have histologically or cytologically confirmed advanced head and neck squamous cell cancer with cutaneous, subcutaneous or nodal tumors deemed as injectable lesions [see definition below] and have measurable disease for the primary study endpoint of overall response rate by RECIST 1.1 and iRECIST.In addition they must have (A) A single measurable tumor at least 1 cm in size and amenable to intratumoral injection or (B) Multiple measurable tumors that in aggregate have a longest diameter of ≥ 10 mm
- Note: Injectable lesion definitions: lesions amenable to percutaneous approach, if technically feasible
- Recurrent and inoperable tumor, progressing after prior radiation with curative-intent for advanced disease (adjuvant or definitive with or without chemotherapy or cetuximab). No prior treatment for local regional recurrence (LRR).
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- Tumors may be either HPV+ or HPV-.
- Tumor must be PD-L1 positive, defined as CPS ≥ 1.
- Be willing to provide tissue; newly obtained biopsy specimens or formalin-fixed, paraffin-embedded (FFPE) block specimens.
- Female subjects of childbearing potential have a negative urine or serum pregnancy test within 7 days prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. It is allowed that the test at the same day at 7 days prior to enrollment. And male / female subjects of childbearing potential must agree to use an adequate method of contraception starting with signing the informed consent through 120 days after the last dose of study medication.
- Demonstrated adequate organ function as defined in following criteria. All screening labs should be performed within 14 days of enrollment. Note: Subject must not have taken transfusion, hematopoietic agent; granulocyte-colony stimulating factor (G-CSF) etc., and/or oxygen supplementation within 7 days before the screening labs.
- Absolute neutrophil count (ANC)>=1,000 /mm3
- Platelets>=100,000 /mm3
- Hemoglobin>=9.0 g/dL
- Serum total bilirubin<=2.0 mg/dL
- Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) <= 2.5x Upper limit of normal (ULN). For subjects with liver metastases<= 5x ULN.
- Serum creatinine<= 1.5 mg/dL; or if serum creatinine >1.5 mg/dL, measured or calculated creatinine/clearance>=60 mL/min (Cockcroft-Gault formula).
- Life expectancy of ≥ 6 months from the first OBP-301 treatment.
- Understand the study requirements and the treatment procedures, and is willing to comply with all specified follow- up evaluations, and provides written informed consent before any study-specific tests or procedures are performed.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy within 2 weeks (chemotherapy, small molecule), or 3 weeks (antibody) of study Day 1.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (greater than the equivalent of prednisone 20 mg/day) or any other form of immunosuppressive therapy within 7 days prior to study Day 1. Daily dose of maintenance prednisone 10mg or equivalent is allowable.
- Has known active central nervous system metastases and/or carcinomatous meningitis.
- Has a known additional malignancy that is progressing or requires active treatment, with the exception of stable/low grade tumors that are not expected to influence life-expectancy (e.g. skin SCC, basal cell, differentiated thyroid cancer, prostate cancer on hormonal therapy).
- Has received a live vaccine within 30 days of planned start of study therapy.
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- Has a known history of Human Immunodeficiency Virus.
- Has known active Hepatitis B or Hepatitis C.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- 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.
- Previous severe hypersensitivity to another monoclonal antibody.
- Has a 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.
- Prior intolerance related to severe (>=grade 3) irAE to a prior anti-immune checkpoint inhibitor agent leading to discontinuation of anti-immune checkpoint inhibitor therapy.
- Any disorder or condition, or any medication that would put the patient at risk from bleeding after direct tumor injection.
- Not a candidate for SBRT given for potentially curative intent. All tumors must receive SBRT. For example, patients with locoregional neck recurrence without significant overlap with the previous radiation field, and who do not warrant SBRT for re-irradiation as per the treating radiation oncologist (e.g. out-of-field recurrence), will not be included in the study.
- Received prior immunotherapy with checkpoint inhibitors or other immunotherapy agents.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Study of OBP-301 (Telomelysin ™) in Combination With Pembrolizumab and Stereotactic Body Irradiation in Patients With Head and Neck Squamous Cell Carcinoma With Inoperable, Recurrent or Progressive Disease
The purpose of this study is to test the effects, of the research study drug Telomelysin (OBP-301) in combination with pembrolizumab in subjects with inoperable, recurrent, or progressive squamous cell carcinoma of the head and neck. Telomelysin is an investigational treatment, while pembrolizumab and SBRT are approved standard treatments. The combination of these three treatments is also considered investigational.
Read the detailed description
This is a phase II open label single arm study of OBP-301 in combination with pembrolizumab and SBRT in advanced HNSCC which is either recurrent and inoperable, or progressing after prior radiation with curative-intent for advanced disease (adjuvant or definitive with or without chemotherapy or cetuximab).
The efficacy of pembrolizumab monotherapy is modest in second or third line of treatment of advanced head and neck cancer (~response rate 16-22%). SBRT reirradiation in patients that received prior surgery and chemoradiation for advanced disease is associated with a response rate (RR) of approximately 60% and approximately 50% 1-year survival. Recently, the results of the Keynote-048 study were published. The projected 1-year survival in the immunotherapy arms with pembrolizumab alone or pembrolizumab and chemotherapy was approximately 57%. So, at present, the benchmark RR for patients with head and neck squamous cell carcinoma with inoperable, recurrent or progressive disease treated with SBRT is approximately 60% and the 1 year survival for patients with head and neck squamous cell carcinoma (HNSCC) with inoperable, recurrent or progressive disease using the most effective contemporary treatments including immunotherapy is approximately 50-57%. Trying to improve the results of the current standard of care, this study will examine the effects of oncolytic virus, OBP-301, administered in addition to pembrolizumab and SBRT in this patient population. The goal of using this triple therapeutic combination is to enhance the chances of cure of the patients.
A total of 36 patients will be enrolled into a two-stage parallel cohort design: In the first stage, 12 patients will be enrolled.
All patients will receive intratumoral injection(s) with OBP-301. If tolerated and no progression is observed, up to twelve injections may be given in each patient.
If the targeted injected lesion(s) disappear, another lesion can be injected at the Investigator's discretion.
A minimum additional 3 doses of concurrent OBP-301 and pembrolizumab will be given if no toxicity, technical impediment to injection or progression is seen.
A maximum total of up to 9 doses of concurrent OBP-301 and pembrolizumab will be given.
Pembrolizumab alone will be continued after day 183 for a total treatment time up to 1 year.
- Being tested
- OBP-301, Pembrolizumab
- Keywords
- Head and Neck, Recurrent, Cure, Unresectable, Immunotherapy, Oncolytic Virus, SBRT, Intratumoral injection
- Medical subject headings
- Disease Progression, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OBP-301Drug
Also called Telomelysin
Telomerase-specific Type 5 Adenovirus. OBP-301 OBP 301 will be injected intratumorally into tumor lesions.
PembrolizumabDrug
Standard dose pembrolizumab 200 mg IV every 3 weeks for up to one year
| Study group | Role | What they receive |
|---|---|---|
| Telomelysin (OBP-301) | Experimental | All patients will receive intratumoral injection(s) with OBP-301. If tolerated and no progression is observed, up to twelve injections may be given in each patient. Receives: Drug: OBP-301; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate, as Assessed by Radiographic Imaging
Examination of patients with a partial response or complete response.
Measured: 30 months
Occurrence of Significant Toxicity, as Measured by Number of Grade 3 and Grade 4 Adverse Events (Combined) Attributable to the Combination of Multiple Intratumoral Injections of OBP-301 With SBRT and Pembrolizumab.
We will measure the rate of grade 3 or 4 adverse events attributed to the combination of multiple intratumoral injections of OBP-301 with SBRT and pembrolizumab.
Measured: 30 months
Secondary outcomes (6)
Disease Control Rate, as Assessed by Radiographic Imaging
Examination of subjects with stable disease, a partial response, or complete response.
Measured: 6 months
Overall Survival, as Measured by the Rate of Survival in Patients
Defined as the time from registration to death from any cause.
Measured: 30 months
Progression Free Survival, as Assessed by Radiographic Imaging and Survival.
Defined as the time from registration to cancer progression or death due to any cause
Measured: 30 months
Duration of Response (DoR), as Measured by Subjects Who Have Responded to Combination Therapy Remain Without Disease Progression
defined as the percentage of patients who have achieved complete response, partial response and stable disease.
Measured: 30 months
Immune Related Response Rate (irRR), as Assessed by Radiographic Imaging
Examination of subjects with stable disease, a partial response, or complete response.Immune-related disease progression (irPD) will be confirmed if the increase in tumor burden is ≥ 25% relative to nadir (minimum recorded tumor burden).
Measured: 30 months
Response in Non-target Lesions, as Assessed by Radiographic Imaging
Examination of patients with a partial response or complete response based on RECIST 1.1 and iRECIST
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2020
- Study start3 May 2021
- Primary completion8 Mar 2022
- Study completion3 Jun 2022
Why it stopped: This study was terminated due to low participant enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck Squamous Cell Carcinoma With Inoperable Recurrent or Progressive DiseaseStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Oncolys BioPharma Inc
- Responsible party
- Sponsor
- Investigators
- Doru Paul, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04685499
- Sponsor's protocol ID
- 19-12021148
- Status last verified
- Dec 2022
- First submitted
- 22 Dec 2020
- Last updated
- 11 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of OBP-301 (Telomelysin ™) in Combination With Pembrolizumab and Stereotactic Body Irradiation in Patients With Head and Neck Squamous Cell Carcinoma With Inoperable, Recurrent or Progressive Disease
- ClinicalTrials.gov ID
- NCT04685499
- Acronym / sponsor ID
- 19-12021148
- Keywords
- Head and Neck, Recurrent, Cure, Unresectable, Immunotherapy, Oncolytic Virus, SBRT, Intratumoral injection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated due to low participant enrollment.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Oncolys BioPharma Inc
- Study start
- 3 May 2021 (actual)
- Primary completion
- 8 Mar 2022 (actual)
- Study completion
- 3 Jun 2022 (actual)
- First posted
- 28 Dec 2020 (actual)
- Results
- Posted 11 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the effects, of the research study drug Telomelysin (OBP-301) in combination with pembrolizumab in subjects with inoperable, recurrent, or progressive squamous cell carcinoma of the head and neck. Telomelysin is an investigational treatment, while pembrolizumab and SBRT are approved standard treatments. The combination of these three treatments is also considered investigational.
Detailed description
This is a phase II open label single arm study of OBP-301 in combination with pembrolizumab and SBRT in advanced HNSCC which is either recurrent and inoperable, or progressing after prior radiation with curative-intent for advanced disease (adjuvant or definitive with or without chemotherapy or cetuximab).
The efficacy of pembrolizumab monotherapy is modest in second or third line of treatment of advanced head and neck cancer (~response rate 16-22%). SBRT reirradiation in patients that received prior surgery and chemoradiation for advanced disease is associated with a response rate (RR) of approximately 60% and approximately 50% 1-year survival. Recently, the results of the Keynote-048 study were published. The projected 1-year survival in the immunotherapy arms with pembrolizumab alone or pembrolizumab and chemotherapy was approximately 57%. So, at present, the benchmark RR for patients with head and neck squamous cell carcinoma with inoperable, recurrent or progressive disease treated with SBRT is approximately 60% and the 1 year survival for patients with head and neck squamous cell carcinoma (HNSCC) with inoperable, recurrent or progressive disease using the most effective contemporary treatments including immunotherapy is approximately 50-57%. Trying to improve the results of the current standard of care, this study will examine the effects of oncolytic virus, OBP-301, administered in addition to pembrolizumab and SBRT in this patient population. The goal of using this triple therapeutic combination is to enhance the chances of cure of the patients.
A total of 36 patients will be enrolled into a two-stage parallel cohort design: In the first stage, 12 patients will be enrolled.
All patients will receive intratumoral injection(s) with OBP-301. If tolerated and no progression is observed, up to twelve injections may be given in each patient.
If the targeted injected lesion(s) disappear, another lesion can be injected at the Investigator's discretion.
A minimum additional 3 doses of concurrent OBP-301 and pembrolizumab will be given if no toxicity, technical impediment to injection or progression is seen.
A maximum total of up to 9 doses of concurrent OBP-301 and pembrolizumab will be given.
Pembrolizumab alone will be continued after day 183 for a total treatment time up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Telomelysin (OBP-301) | Experimental | Drug: OBP-301, Drug: PembrolizumabAll patients will receive intratumoral injection(s) with OBP-301. If tolerated and no progression is observed, up to twelve injections may be given in each patient. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Be >18 years of age on the day of signing the informed consent.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Have histologically or cytologically confirmed advanced head and neck squamous cell cancer with cutaneous, subcutaneous or nodal tumors deemed as injectable lesions [see definition below] and have measurable disease for the primary study endpoint of overall response rate by RECIST 1.1 and iRECIST.In addition they must have (A) A single measurable tumor at least 1 cm in size and amenable to intratumoral injection or (B) Multiple measurable tumors that in aggregate have a longest diameter of ≥ 10 mm
- Note: Injectable lesion definitions: lesions amenable to percutaneous approach, if technically feasible
Key exclusion criteria (18 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy within 2 weeks (chemotherapy, small molecule), or 3 weeks (antibody) of study Day 1.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (greater than the equivalent of prednisone 20 mg/day) or any other form of immunosuppressive therapy within 7 days prior to study Day 1. Daily dose of maintenance prednisone 10mg or equivalent is allowable.
- Has known active central nervous system metastases and/or carcinomatous meningitis.
- Has a known additional malignancy that is progressing or requires active treatment, with the exception of stable/low grade tumors that are not expected to influence life-expectancy (e.g. skin SCC, basal cell, differentiated thyroid cancer, prostate cancer on hormonal therapy).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OBP-301Also: TelomelysinTelomerase-specific Type 5 Adenovirus. OBP-301 OBP 301 will be injected intratumorally into tumor lesions. | Drug | Telomelysin (OBP-301) |
| PembrolizumabStandard dose pembrolizumab 200 mg IV every 3 weeks for up to one year | Drug | Telomelysin (OBP-301) |
Primary outcome
Overall Response Rate, as Assessed by Radiographic Imaging
Time frame: 30 months
Examination of patients with a partial response or complete response.
Occurrence of Significant Toxicity, as Measured by Number of Grade 3 and Grade 4 Adverse Events (Combined) Attributable to the Combination of Multiple Intratumoral Injections of OBP-301 With SBRT and Pembrolizumab.
Time frame: 30 months
We will measure the rate of grade 3 or 4 adverse events attributed to the combination of multiple intratumoral injections of OBP-301 with SBRT and pembrolizumab.
6 secondary outcomes
Disease Control Rate, as Assessed by Radiographic Imaging
Time frame: 6 months
Overall Survival, as Measured by the Rate of Survival in Patients
Time frame: 30 months
Progression Free Survival, as Assessed by Radiographic Imaging and Survival.
Time frame: 30 months
Duration of Response (DoR), as Measured by Subjects Who Have Responded to Combination Therapy Remain Without Disease Progression
Time frame: 30 months
Immune Related Response Rate (irRR), as Assessed by Radiographic Imaging
Time frame: 30 months
Response in Non-target Lesions, as Assessed by Radiographic Imaging
Time frame: 30 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Doru Paul, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OBP-301 and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma With Inoperable Recurrent or Progressive Disease, run by Weill Medical College of Cornell University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate, as Assessed by Radiographic Imaging (time frame: 30 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2023.