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

NCT03409458 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PT-112-103-PAVE-1
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 6

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.

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Keywords

Advanced Solid Tumors; NSCLC; Non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (1)

PT-112 in combination with avelumab

EXPERIMENTAL

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; Biological: avelumab

Interventions

PT-112 DRUG

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.

PT-112 in combination with avelumab

avelumab BIOLOGICAL

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

PT-112 in combination with avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Must provide study-related tumor specimens;
• ECOG(PS) 0-1;
• Estimated Life Expectancy \> 3 months;
• Adequate bone marrow (BM), renal, hepatic and metabolic function.

You may not qualify if:

• 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;
• Known symptomatic central nervous system (CNS) metastases requiring steroids.
• Diagnosis of any other malignancy within 2 years prior to enrollment;
• Vaccination within 4 weeks of the first dose of study treatment is prohibited except for administration of inactivated vaccines;
• Current use of immunosuppressive medication at study entry;
• Active or prior autoimmune disease that might deteriorate with receiving an immunostimulatory agent;
• Acute or chronic infections requiring systemic therapy;
• Known history of autoimmune colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis;
• Known intolerance to checkpoint inhibitor therapy, defined by the occurrence of an AE leading to drug discontinuation;
• Participation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study participation.

Sponsors & Collaborators

• Promontory Therapeutics Inc.: lead
• Pfizer: collaborator
• EMD Serono: collaborator

Study Sites (6)

Arizona

Phoenix, Arizona, 85054, United States

Location

Colorado

Aurora, Colorado, 80045, United States

Location

Florida

Jacksonville, Florida, 32224, United States

Location

Minnesota

Rochester, Minnesota, 55905, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Lausanne

Lausanne, 1011, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Daniel D Karp, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: January 24, 2018
• Study Start: April 24, 2018
• Primary Completion: June 1, 2022
• Study Completion: August 31, 2022
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

CH (1); US (5)