Study of an Immunotherapeutic, DPX-Survivac, in Combination With Low Dose Cyclophosphamide & Pembrolizumab, in Subjects With Selected Advanced & Recurrent Solid Tumors

Immunovaccine

Status and phase: Active, not recruiting; Phase 2

Conditions: Bladder Cancer; Microsatellite Instability-High; Non-small Cell Lung Cancer; Hepatocellular Carcinoma; Ovarian Cancer

Treatments: Other: DPX-Survivac; Drug: Pembrolizumab; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03836352

P1719-SUR-Z11

Keynote 903 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 184 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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184 participants in 2 patient groups

Arm 1 (All cohorts)

Experimental group

Description:

DPX-Survivac, Cyclophosphamide, Pembrolizumab

Treatment:

Drug: Cyclophosphamide

Drug: Pembrolizumab

Other: DPX-Survivac

Arm 2 (Ovarian cohort only)

Experimental group

Description:

DPX-Survivac, Pembrolizumab

Treatment:

Drug: Pembrolizumab

Other: DPX-Survivac