A Study of the Safety and Tolerance of CAN04 in Combination With Pembrolizumab in Subjects With Solid Tumors
Study Details
Study Description
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, 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. Both CAN04 and pembrolizumab will be administered intravenously.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CAN04 and pembrolizumab Subjects will receive weekly doses of CAN04 in combination with pembrolizumab given as standard regimen |
Drug: CAN04
Administered intravenously
Drug: Pembrolizumab
Administered intravenously
|
Outcome Measures
Primary Outcome Measures
- Frequency of TEAEs (treatment-emergent adverse events) [From the first dose until the last subject hast 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) [Up to day 28]
- Number of subjects with grade ≥3 TEAEs [From the first dose until the last subject hast 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 [From the first dose until the last subject hast 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) [From the first dose until the last subject hast 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 [From the first dose until the last subject hast 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 [From the first dose until the last subject hast 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 [From the first dose until the last subject hast 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 [From the first dose until the last subject hast 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 [From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first]
Secondary Outcome Measures
- Serum concentrations of CAN04 and pembrolizumab [From the first dose until the last subject hast 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 hast 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 [From the first dose until the last subject hast 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 [From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first]
- Overall response rate (ORR) [From the first dose until the last subject hast 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)
- Progression free survival [From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first]
- Overall survival [Up to 36 months after 1st dose of last subject (or death)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
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Willing and able to provide intravenous access for the administration of the study drug and for blood sampling/testing.
Exclusion Criteria:
-
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).
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History of uncontrolled brain metastasis.
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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).
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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.
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Subjects with active severe infection requiring oral antibiotics.
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Clinical evidence of an active second invasive malignancy with the exception of stable prostate cancer on watchful waiting.
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Uncontrolled or significant cardiovascular disease.
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History of autoimmune disease requiring systemic immunosuppressive therapy (daily prednisone equivalent doses >10 mg/day).
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HIV patients can be enrolled if the infection is adequately controlled.
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Known bleeding disorder or coagulopathy. Subjects on stable anticoagulant therapy are allowed.
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Known or suspected allergy to study treatment or related products.
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Women who are pregnant or breastfeeding, or trying to become pregnant.
-
Patients with chronic viral hepatitis.
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Colorado Cancer Center | Aurora | Colorado | United States | 80045 |
| 2 | Florida Cancer Specialists & Research Institute | Lake Mary | Florida | United States | 32746 |
| 3 | Hospital of The University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104-5127 |
Sponsors and Collaborators
- Cantargia AB
Investigators
- Study Director: Ignacio Garcia-Ribas, MD, PhD, Chief Medical Officer, Cantargia AB
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CAN04CLIN002