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

NCT04452214 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CAN04CLIN002
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Carcinoma, Non-Small-Cell Lung; Urothelial Carcinoma; Malignant Melanoma; Head and Neck Squamous Cell Carcinoma

Keywords

NSCLC; Adenocarcinoma of lung; Lung cancer; Squamous cell lung cancer; Malignant melanoma; Urothelial cancer; Non-small-cell lung cancer; Non small cell lung cancer; Non-small-cell lung carcinoma; Non small cell lung carcinoma; HNSCC; Head and neck squamous cell carcinoma

Outcome Measures

Primary Outcomes (20)

• Frequency of TEAEs (treatment-emergent adverse events) (Part 1)

  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)

  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)

  Up to day 28

• Number of participants with DLTs (dose-limiting toxicities) (Part 2)

  Up to day 28

• Number of subjects with grade ≥3 TEAEs (Part 1)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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 Outcomes (13)

• Serum concentrations of CAN04 and pembrolizumab (Part 1)

  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)

  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

  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)

  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)

  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

Study Arms (2)

CAN04 and pembrolizumab (Part 1)

EXPERIMENTAL

Subjects will receive weekly doses of CAN04 in combination with pembrolizumab given as standard regimen

Drug: CAN04; Drug: Pembrolizumab

CAN04 + pembrolizumab + carboplatin + pemetrexed (Part 2)

EXPERIMENTAL

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: CAN04; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Pemetrexed

Interventions

CAN04 DRUG

Administered intravenously

CAN04 + pembrolizumab + carboplatin + pemetrexed (Part 2); CAN04 and pembrolizumab (Part 1)

Pembrolizumab DRUG

Administered intravenously

CAN04 + pembrolizumab + carboplatin + pemetrexed (Part 2); CAN04 and pembrolizumab (Part 1)

Carboplatin DRUG

Administered intravenously

CAN04 + pembrolizumab + carboplatin + pemetrexed (Part 2)

Pemetrexed DRUG

Administered intravenously

CAN04 + pembrolizumab + carboplatin + pemetrexed (Part 2)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• Previous therapy with immunotherapy (anti-PD-1, anti-PD-L1, and anti-PD-L2, anti-CTLA-4, or other approved or investigational checkpoint-inhibitors).

Sponsors & Collaborators

• Cantargia AB: lead

Study Sites (3)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Florida Cancer Specialists & Research Institute

Lake Mary, Florida, 32746, United States

Location

Hospital of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104-5127, United States

Location

Related Links

• FDA Safety Alerts and Recalls
• FDA Recalls, Market Withdrawals, and Safety Alerts

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell; Melanoma; Squamous Cell Carcinoma of Head and Neck; Adenocarcinoma of Lung; Lung Neoplasms

Interventions

pembrolizumab; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Adenocarcinoma

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Ignacio Garcia-Ribas, MD, PhD

  Cantargia AB

  STUDY DIRECTOR

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: June 24, 2020
• First Posted: June 30, 2020
• Study Start: September 24, 2020
• Primary Completion: June 28, 2023
• Study Completion: June 28, 2023
• Last Updated: July 14, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)