A Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab (PAVE-1)

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: PT-112; Biological: avelumab

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 Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Lausanne, Switzerland, 1011
    • Lausanne
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Arizona
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Colorado
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Florida
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Minnesota
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PT-112 in combination with 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
NSCLC Cohort: Confirm the RP2D patients with metastatic or locally advanced, squamous or non-squamous NSCLC	24 months
NSCLC Cohort: Assess the safety profile of PT-112 in combination with avelumab	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

Collaborators and Investigators

• Sponsor: Promontory Therapeutics Inc.
• Collaborators: Pfizer; EMD Serono
• Investigators: Principal Investigator: Daniel D Karp, MD, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2018
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (Actual): January 24, 2018

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; Non-small cell lung cancer; Advanced Solid Tumors
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: PT-112-103-PAVE-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No