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

Non-Small Cell Lung Cancer (NSCLC) Clinical Trial

— PAVE-1  

Official title:

A Phase 1b/2a Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03409458
• Other study ID #: PT-112-103-PAVE-1
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 24, 2018
• Est. completion date: August 31, 2022

Study information

• Verified date: November 2023
• Source: Promontory Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: August 31, 2022
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-Small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• PT-112
The RP2D of PT-112 when used in combination with avelumab has been determined during dose escalation and is being confirmed in the NSCLC dose confirmation cohort. For the NSCLC confirmation cohort, PT-112 will be administered at a dose of 360 mg/m2 on Days 1, 8 and 15.

Biological:
• avelumab
Avelumab will be administered at a fixed dose of 800 mg on Days 1 and 15.

Locations

Country	Name	City	State
Switzerland	Lausanne	Lausanne
United States	Colorado	Aurora	Colorado
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Florida	Jacksonville	Florida
United States	Arizona	Phoenix	Arizona
United States	Minnesota	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Promontory Therapeutics Inc.	EMD Serono, Pfizer

Countries where clinical trial is conducted

United States,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	NSCLC Cohort: Confirm the RP2D patients with metastatic or locally advanced, squamous or non-squamous NSCLC		24 months
Secondary	NSCLC Cohort: Assess the safety profile of PT-112 in combination with avelumab		24 months
Secondary	NSCLC Cohort: Evaluate disease control rate (CR, PR and SD lasting =6 months) overall and by tumor type based on iRECIST		24 months
Secondary	NSCLC Cohort: Evaluate disease control rate (CR, PR and SD lasting =3 months) overall and by tumor type based on iRECIST		24 months
Secondary	NSCLC Cohort: Evaluate median duration of response among responding patients		24 months
Secondary	NSCLC Cohort: Evaluate median PFS		24 months
Secondary	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