A Study of MQ710 With and Without Pembrolizumab in People With Solid Tumor Cancer

Study Overview
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Brief Summary
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Participants of this study will have a diagnosis of a solid tumor cancer that has come back to its original location or spread beyond its original location (advanced), came back (relapsed) or worsened (refractory) after standard treatments, or no standard treatments are available for the participants' cancer. The purpose of this study if to find the highest dose of MQ710 that causes few or mild side effects in participants with a solid tumor cancer diagnosis.

Official Title
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A First-In-Human Phase I, Open Label, Safety and Tolerability Study of Escalating Multiple Doses of Intratumoral MQ710, a Multi-Transgene Expressing Modified Vaccinia Virus Ankara-Based Virotherapy, Alone and in Combination With the Systemic Checkpoint Inhibitor Pembrolizumab in Solid Tumors

Conditions
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BCC, Cutaneous Squamous Cell Carcinoma, SCC - Squamous Cell Carcinoma, Basal Cell Carcinoma, BCC - Basal Cell Carcinoma, Melanoma, Merkel Cell Carcinoma, Sebaceous Carcinoma, Extramammary Paget Disease, Kaposi Sarcoma, Head and Neck Squamous Cell Carcinoma, HNSCC, Adnexal Carcinoma, Angiosarcoma, Cutaneous Neoplasm, Advanced Cancer, Metastatic Cancer, Refractory Cancer, Solid Tumor

Intervention / Treatment
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* Biological: MQ719
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or over Histologically or cytologically documented advanced or metastatic cancer that has relapsed from or is refractory to standard treatment in two lines of prior therapy in the advanced setting unless there are fewer than two FDA approved lines of therapy for the particular disease, or for which no standard treatment is available At least 2 tumors suitable for direct or ultrasound-guided injection defined as at least one cutaneous, subcutaneous, or nodal lesion or aggregate of lesions, ≥0.5 cm for any single lesion and cumulative lesion dimensions. One lesion must meet criteria for RECIST measurable disease if in Part 2. Note: One lesion will be biopsied (if possible) Mandatory initial screening biopsy a. For patients undergoing surgical excision/resection: i. Tumor deemed accessible and safe for biopsy by the Investigator ii. Willing to consent to biopsy and surgical procedure iii. Patient able to undergo surgical procedure and appropriate anesthesia b. For patients not undergoing surgical excision/resection to obtain mandatory screening biopsy: i. Tumor deemed accessible and safe for biopsy by the Investigator ii. Willing to consent to initial tumor biopsy Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Patients with no curative treatment options available including surgery and/or definitive radiation or patients in which these modalities are associated with significant morbidity Patients with advanced disease who have received and progressed on standard therapy or have disease for which there is no standard therapy or have contraindications to standard therapy Part 1a: Patients with cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), melanoma, Merkel cell carcinoma, sebaceous carcinoma, extramammary Paget's disease, Kaposi sarcoma, HNSCC, adnexal carcinoma, and angiosarcoma, as well as patients with cutaneous neoplasms that are separate primaries with morbidity from multiple surgeries that have failed standard therapy. Any malignancy with superficial cutaneous or subcutaneous lesions or palpable lymph nodes may be eligible based on the discretion of the investigator. Part 2a: Patients with cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), melanoma, Merkel cell carcinoma, sebaceous carcinoma, extramammary Paget's disease, Kaposi sarcoma, HNSCC, adnexal carcinoma, and angiosarcoma, as well as patients with cutaneous neoplasms that are separate primaries with morbidity from multiple surgeries that have failed standard therapy. BCC will also be included, given that pembrolizumab has not been approved for this condition, although cemiplimab is approved. Parts 1b and 2b: Patients must have cSCC, Merkel cell carcinoma, melanoma, or head and neck squamous cell carcinoma. These patients should be refractory to anti-PD-1 therapy, with the exception of patients with HNSCC with PD-L1 expression <1. Parts 1a, 2a and 2b: Patients with BRAF-mutated melanoma should have received BRAF-targeted therapy. Predicted life expectancy of 3 months or more (in both Part 1 and Part 2) Participant or their legally authorized representative (LAR able to provide written informed consent to participate Ability to comply with study procedures in the Investigator's opinion Adequate renal function as defined by Cr <2 mg/dL Adequate hepatic function Serum bilirubin ≤1.5 x ULN AST and ALT ≤2.5 ULN (no liver mets) AST and ALT ≤5.0 ULN (for patients with liver mets) Adequate bone marrow and hematologic function Coagulation function adequate (PT and aPTT within x1.5 ULN) Platelets ≥ 75,000/mm^2 ANC ≥ 1000/uL Females of child-bearing potential must have a negative pregnancy test within 14 days prior to enrollment and on day of treatment. All patients must agree to use adequate contraception prior to study entry, for the duration of study participation, and up to 90 days after the last dose of MQ710 Part 2 only: at least one measurable site of disease according to RECIST criteria Prior non-immunotherapy, anti-tumor treatment including endocrine, chemical/radiotherapy, targeted therapy, or major surgery (but not anti-PD1/- L1 therapies) was discontinued for more than 4 weeks prior to enrollment Patients who have failed prior anti-PD1/-PDL1 may be included. Washout of anti-PD1/-PDL1 at least 3 weeks prior to initiation of therapy in Part 1a and 2a. No washout period is required for Part 1b and 2b. Exclusion Criteria: Splenectomy Active infections requiring antibiotics, physician monitoring or recurrent fevers (>38.0 ℃) associated with a clinical diagnosis of active infection Acute or chronic active viral disease or positive test for hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), or received treatment with antivirals or nucleoside analogs such as those used in the treatment of hepatitis B (e.g. lamivudine, adefovir, tenofovir, telbivudine, entecavir), ribavirin, cidofovir, diaminopurine analogs, methyladenosine analogs, or interferon alpha within 4 weeks of initiation of study treatment Incomplete recovery from surgery, incomplete healing of an incision site Any of the following in the 3 months before the first dose of study treatment: Grade 3 or 4 gastrointestinal bleeding/haemorrhage (unless due to resected tumour), treatment-resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thrombo-embolic event, history or evidence of haemoptysis or menorrhagia History of myocardial infarction, myocarditis, congestive heart failure (as defined by New York Heart Association Functional Classsification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia,or significant cardiovascular or cerebrovascular event in the 6 months before the first dose of study treatment Uncontrolled infection within 6 months prior to study entry. History of significant bleeding requiring hospitalization in the 12 months before the first dose of study treatment Treatment with PD-1/programmed death ligand (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), or any other (including experimental) immune checkpoint inhibitor or immune-stimulatory treatment in the 3 weeks before the first dose of study treatment Prior chemotherapy, radiotherapy, biological cancer therapy (not including anti-PD1/-L1 immunotherapies), targeted therapy, investigational drug, or major surgery 28 days prior to enrollment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment with the exception of grade 2 or better for alopecia and neuropathy. Has known active CNS metastases and/or carcinomatous meningitis Received live vaccine within 28 days prior to enrollment Patient is pregnant or breast-feeding, or expecting to conceive or father children within the duration of the trial Patients with tumor that directly contacts, encases or penetrates a major blood vessel, pericardium, gastrointestinal tract, or other hollow organs that may lead to perforation due to tumor necrosis Patients at risk of airway compromise in the event of post-injection tumor swelling/inflammation based on investigator judgement History or evidence of autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) History of chronic liver disease or evidence of hepatic cirrhosis History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia, active interstitial lung disease (ILD) requiring treatment with systemic steroids Baseline pulse oximetry less than 92% on room air History of re-irradiation to a field which includes the carotid arteries History of leukemia: ALL and CLL (patients with a history of aggressive lymphomas in remission or patients with a history of allogeneic stem cell transplants are eligible if no longer on immunosuppressive therapy and without evidence of GvHD) Current use of steroids such as prednisone 10 mg/daily or greater (or its equivalent) or immunosupressants within 2 weeks of initiation of study treatment Any serious or uncontrolled medical disorder that, in the opinion of the Investigator or the Medical Monitor, may increase the risk associated with study participation or study treatment administration, impair the ability of the patient to receive protocol therapy or interfere with the interpretation of study results Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent Known allergy to MQ710 transgene products or formulation. Patient requires anticoagulation therapy, such as warfarin.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Group<br>MQ710 The dose levels will be escalated following a standard 3+3 dose escalation scheme. | Biological: MQ719<br>* Patients will receive either multidose monotherapy with MQ710 or multidose combination therapy with MQ710 and pembrolizumab. The applicable dose of MQ710 will be injected directly into the patient's tumor (intratumorally), and standard dosing of pembrolizumab (200 mg) will be administered intravenously at a 3-week interval.<br>|
| Experimental: Dose Expansion Group<br>MQ710 + pembrolizumab Approximately 8 patients will be recruited into the dose expansion group for monotherapy dosing of MQ710. Approximately 12 patients will be recruited for dosing at the MTD/maximally administered dose established in combination with pembrolizumab. | Biological: MQ719<br>* Patients will receive either multidose monotherapy with MQ710 or multidose combination therapy with MQ710 and pembrolizumab. The applicable dose of MQ710 will be injected directly into the patient's tumor (intratumorally), and standard dosing of pembrolizumab (200 mg) will be administered intravenously at a 3-week interval.<br>Drug: Pembrolizumab<br>* Patients will receive either multidose monotherapy with MQ710 or multidose combination therapy with MQ710 and pembrolizumab. The applicable dose of MQ710 will be injected directly into the patient's tumor (intratumorally), and standard dosing of pembrolizumab (200 mg) will be administered intravenously at a 3-week interval.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of MQ710 by review of AEs and SAEs | Review the safety and tolerability of MQ710 by review of AE's and SAE's by CTCAE v 5.0 | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cutaneous Squamous Cell Carcinoma, SCC - Squamous Cell Carcinoma, Basal Cell Carcinoma, Melanoma, Merkel Cell Carcinoma, Sebaceous Carcinoma, Extramammary Paget Disease, Kaposi Sarcoma, Head and Neck Squamous Cell Carcinoma, HNSCC, Adnexal Carcinoma, Angiosarcoma, Cutaneous Neoplasm, Advanced Cancer, Metastatic Cancer, Refractory Cancer, MQ710, Memorial Sloan Kettering Cancer Center, 22-278, Solid Tumor, BCC