A Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab

Phase 1

Completed

• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Interventions: Drug: PT-112; Biological: avelumab

• Registration Number: NCT03409458
• Lead Sponsor: Promontory Therapeutics Inc.

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.

Study Timeline

• Study First Submitted: 2018-01-18
• Study First Submitted QC: 2018-01-23
• Study First Posted: 2018-01-24
• Study Start: 2018-04-24
• Primary Completion: 2022-06-01
• Study Completion: 2022-08-31
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-15
• Last Update Posted: 2023-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PT-112 in combination with avelumab	PT-112	PT-112, administered by intravenous infusion avelumab, administered by intravenous infusion Patients with all listed conditions are eligible for treatment during the dose escalation phase of the study. Patients with NSCLC are eligible for the dose confirmation phase of the study.
PT-112 in combination with avelumab	avelumab	PT-112, administered by intravenous infusion avelumab, administered by intravenous infusion Patients with all listed conditions are eligible for treatment during the dose escalation phase of the study. Patients with NSCLC are eligible for the dose confirmation phase of the study.

Primary Outcome Measures

Name	Time	Method
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.	24 months

Secondary Outcome Measures

Name	Time	Method
NSCLC Cohort: Assess the safety profile of PT-112 in combination with avelumab	24 months
NSCLC Cohort: Confirm the RP2D patients with metastatic or locally advanced, squamous or non-squamous NSCLC	24 months
NSCLC Cohort: Evaluate disease control rate (CR, PR and SD lasting ≥6 months) overall and by tumor type based on iRECIST	24 months
NSCLC Cohort: Evaluate disease control rate (CR, PR and SD lasting ≥3 months) overall and by tumor type based on iRECIST	24 months
NSCLC Cohort: Evaluate median duration of response among responding patients	24 months
NSCLC Cohort: Evaluate median PFS	24 months
NSCLC Cohort: Evaluate PFS rate at 6 months from start of study drug, based on tumor assessments every 8 weeks based on iRECIST	24 months

Trial Locations

Locations (6)

Colorado; 🇺🇸 Aurora, Colorado, United States

Arizona; 🇺🇸 Phoenix, Arizona, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Florida; 🇺🇸 Jacksonville, Florida, United States

Minnesota; 🇺🇸 Rochester, Minnesota, United States

Lausanne; 🇨🇭 Lausanne, Switzerland