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.

Age: 18 Years and older

Gender: All

Start Date: 12/21/2018

Primary Completion Date (Estimated): 12/31/2023

Study Completion Date (Estimated): 12/31/2023

Accepts Healthy Volunteers: No

Trial Purpose and 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.

Eligibility Criteria

Age: 18 Years and older

Gender: All

Accepts Healthy Volunteers: No

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