Brief Summary
This study will assess the safety and efficacy of DPX-Survivac and low dose cyclophosphamide with pembrolizumab in subjects with selected advanced and recurrent solid tumours.
Brief Title
Study of an Immunotherapeutic, DPX-Survivac, in Combination With Low Dose Cyclophosphamide & Pembrolizumab, in Subjects With Selected Advanced & Recurrent Solid Tumors
Detailed Description
This study is a Phase 2 with safety lead-in study to assess the safety and efficacy of DPX-Survivac, low dose cyclophosphamide, and pembrolizumab combination therapy in subjects with selected advanced and recurrent solid tumours. Two ovarian cancer arms will be recruited and randomized in this study, one with and one without cyclophosphamide. All other cohorts will be single arm, receiving treatment with the triple combination.
Up to 20 subjects, from any cohort, will be enrolled to assess the safety of study treatments before the study moves to the expansion phase. Once the safety lead-in is completed, the five cohorts will be expanded to recruit additional subjects following a Simon two stage design. Enrollment in the ovarian cancer cohort will be randomized 1:1 into two arms.
Up to 20 subjects, from any cohort, will be enrolled to assess the safety of study treatments before the study moves to the expansion phase. Once the safety lead-in is completed, the five cohorts will be expanded to recruit additional subjects following a Simon two stage design. Enrollment in the ovarian cancer cohort will be randomized 1:1 into two arms.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Ovarian Cancer
Hepatocellular Carcinoma
Non-small Cell Lung Cancer
Bladder Cancer
Microsatellite Instability-High
Eligibility Criteria
Key Inclusion Criteria:
* Subjects with advanced or metastatic solid tumours who have completed treatment with first line therapy:
1. Epithelial ovarian, fallopian tube, or peritoneal cancer
2. Hepatocellular carcinoma
3. Non-small cell lung cancer
4. Urothelial cancer
5. Microsatellite instability high solid tumours, other than the above indications
* Radiologic and/or biochemical evidence of disease progression
* Completion of pre-treatment tumour biopsy
* Must have measurable disease by RECIST v1.1
* Ambulatory with an ECOG 0-1
* Life expectancy ≥ 6 months
* Meet protocol-specified laboratory requirements
Key Exclusion Criteria:
* Chemotherapy or immunotherapy within treatment within 28 days of start of study treatment
* Radiotherapy within treatment within 2 weeks of start of study treatment
* Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor where subject was discontinued from that treatment due to a Grade 3 or higher immune-related toxicity
* For NSCLC subjects: Known EGFR mutations or ALK rearrangements
* Prior receipt of survivin-based vaccine(s) and/or immunotherapies
* Concurrent second malignancy other than non-melanoma skin cancer, cervical carcinoma in situ, or controlled bladder cancer
* Clinical ascites or pleural fluid that cannot be managed
* Malignant bowel obstruction or recent history of bowel obstruction
* For OvCa, subjects with any single lesion greater than 5 cm
* Autoimmune disease requiring treatment within the last two years (except replacement therapy)
* Recent history of thyroiditis
* Any history of (non-infectious) pneumonitis that required steroid therapy or current pneumonitis
* Presence of a serious acute or chronic infection
* Active CNS metastases and/or carcinomatous meningitis
* GI condition that might limit absorption of oral agents
* Allogenic tissue/solid organ transplant
* Other serious intercurrent chronic or acute illness, including myocardial infarction or cerebrovascular event within 6 months
* Ongoing treatment with steroid therapy or other immunosuppressive
* Receipt of live attenuated vaccines
* Acute or chronic skin and/or microvascular disorders
* Edema or lymphedema in the lower limbs \> grade 2
* Severe hypersensitivity (≥ Grade 3) to pembrolizumab
* Subjects with advanced or metastatic solid tumours who have completed treatment with first line therapy:
1. Epithelial ovarian, fallopian tube, or peritoneal cancer
2. Hepatocellular carcinoma
3. Non-small cell lung cancer
4. Urothelial cancer
5. Microsatellite instability high solid tumours, other than the above indications
* Radiologic and/or biochemical evidence of disease progression
* Completion of pre-treatment tumour biopsy
* Must have measurable disease by RECIST v1.1
* Ambulatory with an ECOG 0-1
* Life expectancy ≥ 6 months
* Meet protocol-specified laboratory requirements
Key Exclusion Criteria:
* Chemotherapy or immunotherapy within treatment within 28 days of start of study treatment
* Radiotherapy within treatment within 2 weeks of start of study treatment
* Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor where subject was discontinued from that treatment due to a Grade 3 or higher immune-related toxicity
* For NSCLC subjects: Known EGFR mutations or ALK rearrangements
* Prior receipt of survivin-based vaccine(s) and/or immunotherapies
* Concurrent second malignancy other than non-melanoma skin cancer, cervical carcinoma in situ, or controlled bladder cancer
* Clinical ascites or pleural fluid that cannot be managed
* Malignant bowel obstruction or recent history of bowel obstruction
* For OvCa, subjects with any single lesion greater than 5 cm
* Autoimmune disease requiring treatment within the last two years (except replacement therapy)
* Recent history of thyroiditis
* Any history of (non-infectious) pneumonitis that required steroid therapy or current pneumonitis
* Presence of a serious acute or chronic infection
* Active CNS metastases and/or carcinomatous meningitis
* GI condition that might limit absorption of oral agents
* Allogenic tissue/solid organ transplant
* Other serious intercurrent chronic or acute illness, including myocardial infarction or cerebrovascular event within 6 months
* Ongoing treatment with steroid therapy or other immunosuppressive
* Receipt of live attenuated vaccines
* Acute or chronic skin and/or microvascular disorders
* Edema or lymphedema in the lower limbs \> grade 2
* Severe hypersensitivity (≥ Grade 3) to pembrolizumab
Inclusion Criteria
Inclusion Criteria:
* Subjects with advanced or metastatic solid tumours who have completed treatment with first line therapy:
1. Epithelial ovarian, fallopian tube, or peritoneal cancer
2. Hepatocellular carcinoma
3. Non-small cell lung cancer
4. Urothelial cancer
5. Microsatellite instability high solid tumours, other than the above indications
* Radiologic and/or biochemical evidence of disease progression
* Completion of pre-treatment tumour biopsy
* Must have measurable disease by RECIST v1.1
* Ambulatory with an ECOG 0-1
* Life expectancy ≥ 6 months
* Meet protocol-specified laboratory requirements
* Subjects with advanced or metastatic solid tumours who have completed treatment with first line therapy:
1. Epithelial ovarian, fallopian tube, or peritoneal cancer
2. Hepatocellular carcinoma
3. Non-small cell lung cancer
4. Urothelial cancer
5. Microsatellite instability high solid tumours, other than the above indications
* Radiologic and/or biochemical evidence of disease progression
* Completion of pre-treatment tumour biopsy
* Must have measurable disease by RECIST v1.1
* Ambulatory with an ECOG 0-1
* Life expectancy ≥ 6 months
* Meet protocol-specified laboratory requirements
Gender
All
Gender Based
false
Keywords
T cell activation
Immunotherapy
Ovarian
Hepatocellular Carcinoma
Non-small Cell Lung
Bladder
Microsatellite Instability-High
Survivin
Anti-PD-1
MK-3475
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03836352
Org Class
Industry
Org Full Name
ImmunoVaccine Technologies, Inc. (IMV Inc.)
Org Study Id
P1719-SUR-Z11
Overall Status
Active, not recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment, DPX-Survivac in Combination With Low Dose Cyclophosphamide and Pembrolizumab, in Subjects With Selected Advanced and Recurrent Solid Tumours.
Primary Outcomes
Outcome Description
Centrally evaluated using RECIST v1.1
Outcome Measure
Efficacy as measured by objective response rate
Outcome Time Frame
Approximately 24 months
Outcome Description
Using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Outcome Measure
Safety as measured by the rate of adverse events
Outcome Time Frame
Approximately 24 months
Secondary Ids
Secondary Id
Keynote 903
Secondary Outcomes
Outcome Description
Centrally evaluated using iRECIST
Outcome Time Frame
Approximately 24 months
Outcome Measure
Objective response rate
Outcome Time Frame
Approximately 24 months
Outcome Measure
Duration of response
Outcome Time Frame
Approximately 24 months
Outcome Measure
Disease control rate
Outcome Time Frame
Approximately 24 months
Outcome Measure
Progression Free Survival
Outcome Time Frame
Approximately 24 months
Outcome Measure
Overall survival
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Andreas Kaubisch
Investigator Email
akaubisc@montefiore.org
Investigator Phone
718-920-7100
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Endocrine System Cancers --- ENDOCRINE GLAND NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Prostate Cancer --- UROGENITAL NEOPLASMS
Endocrine System Cancers --- ENDOCRINE SYSTEM DISEASES
Diabetes --- ENDOCRINE SYSTEM DISEASES
Diabetes & Endocrine System --- ENDOCRINE SYSTEM DISEASES
Endocrine System Cancers --- ADENOCARCINOMA
Cancer --- CARCINOMA
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Digestive System --- LIVER DISEASES
Liver --- LIVER DISEASES
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
Kidney & Urinary Tract --- URINARY BLADDER DISEASES
Kidney & Urinary Tract --- UROLOGIC DISEASES
MeSH Terms
OVARIAN NEOPLASMS
CARCINOMA, HEPATOCELLULAR
CARCINOMA, NON-SMALL-CELL LUNG
URINARY BLADDER NEOPLASMS
ENDOCRINE GLAND NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
OVARIAN DISEASES
ADNEXAL DISEASES
GENITAL DISEASES, FEMALE
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
GENITAL NEOPLASMS, FEMALE
UROGENITAL NEOPLASMS
GENITAL DISEASES
ENDOCRINE SYSTEM DISEASES
GONADAL DISORDERS
ADENOCARCINOMA
CARCINOMA
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS BY HISTOLOGIC TYPE
LIVER NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
DIGESTIVE SYSTEM DISEASES
LIVER DISEASES
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
UROLOGIC NEOPLASMS
URINARY BLADDER DISEASES
UROLOGIC DISEASES
MALE UROGENITAL DISEASES
CYCLOPHOSPHAMIDE
PEMBROLIZUMAB
PHOSPHORAMIDE MUSTARDS
NITROGEN MUSTARD COMPOUNDS
MUSTARD COMPOUNDS
HYDROCARBONS, HALOGENATED
HYDROCARBONS
ORGANIC CHEMICALS
PHOSPHORAMIDES
ORGANOPHOSPHORUS COMPOUNDS