A Study of the Safety and Tolerance of CAN04 and Pembrolizumab in Combination With and Without Carboplatin and Pemetrexed in Subjects With Solid Tumors

July 13, 2023 updated by: Cantargia AB

An Open-label, Safety and Tolerability Phase 1b Trial of CAN04, a Fully Humanized Anti-IL1RAP Monoclonal Antibody, and Pembrolizumab in Combination With and Without Carboplatin and Pemetrexed in Subjects With Solid Tumors

This study will consider the safety and effectiveness of a study drug, CAN04, in combination with pembrolizumab, in the treatment of incurable or metastatic non-small-cell lung cancer (NSCLC), head and neck squamous cell carcinoma, urothelial cancer, or malignant melanoma. The study aims to establish a recommended dose of CAN04 in combination with the standard dose of pembrolizumab (Part 1), and in combination with pembrolizumab standard dose, and Standard of Care carboplatin and pemetrexed (Part 2 - subjects with stage IV, non-squamous metastatic NSCLC). CAN04, pembrolizumab. carboplatin and pemetrexed will be administered intravenously.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center
    • Florida
      • Lake Mary, Florida, United States, 32746
        • Florida Cancer Specialists & Research Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-5127
        • Hospital of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria (Part 1):

  • Subjects with metastatic or locally advanced, incurable non-small-cell lung cancer (NSCLC [adenocarcinoma, adenosquamous, or squamous]), head and neck squamous cell carcinoma (HNSCC), urothelial cancer, or malignant melanoma who have exhausted or declined available standard therapy.
  • Subjects progressing on previous treatment with a checkpoint inhibitor targeting thePD-1/PD-L1 pathway, alone or in combination with chemotherapy after previously having achieved stable disease or better and stayed on such therapy for ≥12 weeks.
  • Primary or metastatic lesion suitable for biopsy and willingness to undergo repeat biopsies as appropriate.
  • Willing and able to provide intravenous access for the administration of the study drug and for blood sampling/testing.

Inclusion Criteria (Part 2):

  • Subjects with histologically confirmed non-squamous metastatic (stage IV) NSCLC, without option for locoregional treatment with curative intent.
  • Subjects who have not received prior systemic anti-cancer therapy for the locally advanced or metastatic NSCLC. Subjects who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease.
  • Ability to safety undergo pre-treatment (if no archival biopsy is available) and on-treatment tumor biopsies.
  • Subject consents to retrieval of archival tumor tissue for screening in case no fresh biopsy is performed during screening.
  • Willing and able to provide intravenous access for the administration of the study drug and for blood sampling/testing.

Exclusion Criteria (Parts 1 and 2):

  • Subjects with NSCLC tumors with genetic alteration or mutation, for which FDA-approved targeted therapy is available.
  • Treatment with systemic anticancer treatments, investigational products, or major surgery within 4 weeks before first dose of study drug or 5 half-lives, whichever is shorter. Subjects should have recovered from previous treatment toxicity (except hair loss and peripheral neuropathy).
  • History of uncontrolled brain metastasis.
  • Subject has received extended field radiotherapy ≤4 weeks before the start of treatment (≤2 weeks for limited field radiation to alleviate symptoms), and who has not recovered from related side effects of such therapy (except for hair loss).
  • Subjects who have previously experienced an immune-related adverse event (irAE) to pembrolizumab, for which permanent discontinuation is required. Subjects without a formal contraindication due to previous irAE are not eligible if the AE has not resolved or requires steroids (>10 mg prednisone-equivalent per day) for ongoing management.
  • Subjects with active severe infection requiring oral antibiotics.
  • Clinical evidence of an active second invasive malignancy with the exception of stable prostate cancer on watchful waiting.
  • Uncontrolled or significant cardiovascular disease.
  • History of autoimmune disease requiring systemic immunosuppressive therapy (daily prednisone equivalent doses >10 mg/day).
  • HIV patients can be enrolled if the infection is adequately controlled.
  • Known bleeding disorder or coagulopathy. Subjects on stable anticoagulant therapy are allowed.
  • Known or suspected allergy to study treatment or related products.
  • Women who are pregnant or breastfeeding, or trying to become pregnant.
  • Patients with chronic viral hepatitis.

Exclusion criteria (Part 2):

  • Previous therapy with immunotherapy (anti-PD-1, anti-PD-L1, and anti-PD-L2, anti-CTLA-4, or other approved or investigational checkpoint-inhibitors).
  • Subject is unable or unwilling to take folic acid or vitamin B12 supplementation.
  • Subject is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDS), other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CAN04 and pembrolizumab (Part 1)
Subjects will receive weekly doses of CAN04 in combination with pembrolizumab given as standard regimen
Drug: Pembrolizumab
Administered intravenously
Drug: CAN04
Administered intravenously
Experimental: CAN04 + pembrolizumab + carboplatin + pemetrexed (Part 2)
Subjects will receive doses of CAN04 on Days 1 and 8 (Cycles 1 thru 4), and on Day 1 (Cycle 5 onwards) in combination with pembrolizumab given as standard regimen and carboplatin and pemetrexed standard of care
Drug: Carboplatin
Administered intravenously
Drug: Pembrolizumab
Administered intravenously
Drug: Pemetrexed
Administered intravenously
Drug: CAN04
Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency of TEAEs (treatment-emergent adverse events) (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Frequency of TEAEs (treatment-emergent adverse events) (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Number of participants with DLTs (dose-limiting toxicities) (Part 1)
Time Frame: Up to day 28
Up to day 28
Number of participants with DLTs (dose-limiting toxicities) (Part 2)
Time Frame: Up to day 28
Up to day 28
Number of subjects with grade ≥3 TEAEs (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Number of subjects with grade ≥3 TEAEs (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Percentage of subjects with grade ≥3 TEAEs (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Percentage of subjects with grade ≥3 TEAEs (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Number of subjects with 1 or more SAEs (serious adverse events) (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Number of subjects with 1 or more SAEs (serious adverse events) (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Percentage of subjects with 1 or more SAEs (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Percentage of subjects with 1 or more SAEs (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Number of subjects with 1 or more TEAEs leading to dose modifications (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Number of subjects with 1 or more TEAEs leading to dose modifications (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Number of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Number of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Percentage of subjects with 1 or more TEAEs leading to dose modifications (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Percentage of subjects with 1 or more TEAEs leading to dose modifications (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Percentage of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Percentage of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum concentrations of CAN04 and pembrolizumab (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Serum concentrations of CAN04 and pembrolizumab (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Antidrug antibodies (ADAs) against CAN04
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Change in serum IL-6 (interleukin-6) concentration (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Change in serum IL-6 (interleukin-6) concentration (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Change in serum CRP (C-reactive protein) concentration (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Change in serum CRP (C-reactive protein) concentration (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Overall response rate (ORR) (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Proportion of subjects with partial response (PR) or complete response (CR) to study treatment as defined by iRECIST (immune-related response evaluation criteria in solid tumors) and measured by radiological assessment (CT/MRI scan)
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Overall response rate (ORR) (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Proportion of subjects with partial response (PR) or complete response (CR) to study treatment as defined by iRECIST (immune-related response evaluation criteria in solid tumors) and measured by radiological assessment (CT/MRI scan)
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Progression free survival (Part 1)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Progression free survival (Part 2)
Time Frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first
Overall survival (Part 1)
Time Frame: Up to 36 months after 1st dose of last subject (or death)
Up to 36 months after 1st dose of last subject (or death)
Overall survival (Part 2)
Time Frame: Up to 36 months after 1st dose of last subject (or death)
Up to 36 months after 1st dose of last subject (or death)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cantargia AB

Investigators

  • Study Director: Ignacio Garcia-Ribas, MD, PhD, Cantargia AB

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 24, 2020

Primary Completion (Actual)

June 28, 2023

Study Completion (Actual)

June 28, 2023

Study Registration Dates

First Submitted

June 24, 2020

First Submitted That Met QC Criteria

June 28, 2020

First Posted (Actual)

June 30, 2020

Study Record Updates

Last Update Posted (Actual)

July 14, 2023

Last Update Submitted That Met QC Criteria

July 13, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAN04CLIN002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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