Clinical trial NCT03409458: A Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab
Official title: A Phase 1b/2a Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Keywords: Advanced Solid Tumors
NSCLC
Non-small cell lung cancer
Lead sponsor: Promontory Therapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
name: EMD Serono
First posted: 2018-01-24
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 1/2, open-label, multi-center, non-randomized, dose-escalation study of PT-112 in combination with the anti-PD-L1 antibody, avelumab, in selected advanced solid tumors.

The study is to be conducted in two parts: the Dose Escalation Phase of PT-112 within the combination and the Dose Confirmation Phase in patients with non-small cell lung cancer who will be treated at the RP2D.

Detailed description: This is a Phase 1/2, open-label, multi-center, non-randomized, dose-escalation study of PT-112 in combination with the anti-PD-L1 antibody, avelumab, in selected advanced solid tumors. The study is to be conducted in two parts: the Dose Escalation Phase and the Dose Confirmation Phase.

Enrollment for dose escalation and dose confirmation is complete.

Eligibility criteria: Key Inclusion Criteria:

1. Histologically or cytologically confirmed metastatic or locally advanced, squamous or non-squamous NSCLC (NSCLC). Patients must have received no more than four prior lines of therapy, including a PD-1 / PD-L1-containing therapy and a platinum containing regimen. Patients must have received no more than one taxane containing regimen and no more than one investigational agent;
2. Must provide study-related tumor specimens;
3. ECOG(PS) 0-1;
4. Estimated Life Expectancy \> 3 months;
5. Adequate bone marrow (BM), renal, hepatic and metabolic function.

Key Exclusion Criteria:

1. Concurrent cancer treatment with cytoreductive therapy, radiotherapy, cytokine therapy, cytotoxic agents, targeted small molecule therapy or any investigational anticancer small molecule drugs within 2 weeks prior to the start of study treatment (except 5 weeks from last dose of nitrosourea compound) OR treatment with monoclonal antibodies within 4 weeks prior to the start of study treatment;
2. Known symptomatic central nervous system (CNS) metastases requiring steroids.
3. Diagnosis of any other malignancy within 2 years prior to enrollment;
4. Vaccination within 4 weeks of the first dose of study treatment is prohibited except for administration of inactivated vaccines;
5. Current use of immunosuppressive medication at study entry;
6. Active or prior autoimmune disease that might deteriorate with receiving an immunostimulatory agent;
7. Acute or chronic infections requiring systemic therapy;
8. Known history of autoimmune colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis;
9. Known intolerance to checkpoint inhibitor therapy, defined by the occurrence of an AE leading to drug discontinuation;
10. Participation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study participation.

Primary outcomes:
measure: NSCLC Cohort: Evaluate best overall response rate (ORR) by tumor type according to Immune-Response Criteria (iRECIST) in metastatic or locally advanced, squamous or non-squamous NSCLC.
timeFrame: 24 months
Secondary outcomes:
measure: NSCLC Cohort: Confirm the RP2D patients with metastatic or locally advanced, squamous or non-squamous NSCLC
timeFrame: 24 months
measure: NSCLC Cohort: Assess the safety profile of PT-112 in combination with avelumab
timeFrame: 24 months
measure: NSCLC Cohort: Evaluate disease control rate (CR, PR and SD lasting ≥6 months) overall and by tumor type based on iRECIST
timeFrame: 24 months
measure: NSCLC Cohort: Evaluate disease control rate (CR, PR and SD lasting ≥3 months) overall and by tumor type based on iRECIST
timeFrame: 24 months
measure: NSCLC Cohort: Evaluate median duration of response among responding patients
timeFrame: 24 months
measure: NSCLC Cohort: Evaluate median PFS
timeFrame: 24 months
measure: NSCLC Cohort: Evaluate PFS rate at 6 months from start of study drug, based on tumor assessments every 8 weeks based on iRECIST
timeFrame: 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona
state: Arizona
city: Aurora
country: United States
facility: Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Florida
state: Florida
city: Rochester
country: United States
facility: Minnesota
state: Minnesota
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Lausanne
country: Switzerland
facility: Lausanne
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Daniel D Karp, MD
role: PRINCIPAL_INVESTIGATOR
References: