Clinical trial NCT04452214: A Study of the Safety and Tolerance of CAN04 and Pembrolizumab in Combination With and Without Carboplatin and Pemetrexed in Subjects With Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Cantargia AB
Sponsor class: INDUSTRY
First posted: 2020-06-30
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of TEAEs (treatment-emergent adverse events) (Part 1)
timeFrame: 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
measure: Frequency of TEAEs (treatment-emergent adverse events) (Part 2)
timeFrame: 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
measure: Number of participants with DLTs (dose-limiting toxicities) (Part 1)
timeFrame: Up to day 28
measure: Number of participants with DLTs (dose-limiting toxicities) (Part 2)
timeFrame: Up to day 28
measure: Number of subjects with grade ≥3 TEAEs (Part 1)
timeFrame: 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
measure: Number of subjects with grade ≥3 TEAEs (Part 2)
timeFrame: 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
measure: Percentage of subjects with grade ≥3 TEAEs (Part 1)
timeFrame: 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
measure: Percentage of subjects with grade ≥3 TEAEs (Part 2)
timeFrame: 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
measure: Number of subjects with 1 or more SAEs (serious adverse events) (Part 1)
timeFrame: 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
measure: Number of subjects with 1 or more SAEs (serious adverse events) (Part 2)
timeFrame: 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
measure: Percentage of subjects with 1 or more SAEs (Part 1)
timeFrame: 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
measure: Percentage of subjects with 1 or more SAEs (Part 2)
timeFrame: 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
measure: Number of subjects with 1 or more TEAEs leading to dose modifications (Part 1)
timeFrame: 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
measure: Number of subjects with 1 or more TEAEs leading to dose modifications (Part 2)
timeFrame: 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
measure: Number of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 1)
timeFrame: 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
measure: Number of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 2)
timeFrame: 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
measure: Percentage of subjects with 1 or more TEAEs leading to dose modifications (Part 1)
timeFrame: 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
measure: Percentage of subjects with 1 or more TEAEs leading to dose modifications (Part 2)
timeFrame: 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
measure: Percentage of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 1)
timeFrame: 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
measure: Percentage of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 2)
timeFrame: 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:
measure: Serum concentrations of CAN04 and pembrolizumab (Part 1)
timeFrame: 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
measure: Serum concentrations of CAN04 and pembrolizumab (Part 2)
timeFrame: 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
measure: Antidrug antibodies (ADAs) against CAN04
timeFrame: 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
measure: Change in serum IL-6 (interleukin-6) concentration (Part 1)
timeFrame: 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
measure: Change in serum IL-6 (interleukin-6) concentration (Part 2)
timeFrame: 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
measure: Change in serum CRP (C-reactive protein) concentration (Part 1)
timeFrame: 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
measure: Change in serum CRP (C-reactive protein) concentration (Part 2)
timeFrame: 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
measure: Overall response rate (ORR) (Part 1)
timeFrame: 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
measure: Overall response rate (ORR) (Part 2)
timeFrame: 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
measure: Progression free survival (Part 1)
timeFrame: 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
measure: Progression free survival (Part 2)
timeFrame: 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
measure: Overall survival (Part 1)
timeFrame: Up to 36 months after 1st dose of last subject (or death)
measure: Overall survival (Part 2)
timeFrame: Up to 36 months after 1st dose of last subject (or death)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Lake Mary
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Philadelphia
country: United States
facility: Hospital of The University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Cantargia AB
name: Ignacio Garcia-Ribas, MD, PhD
role: STUDY_DIRECTOR
References: