Brief Title: A Study of the Safety and Tolerance of CAN04 in Combination With Pembrolizumab in Subjects With Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Frequency of TEAEs (treatment-emergent adverse events) (Part 1)

Primary Outcome 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

Primary Outcome 2 - Measure: Frequency of TEAEs (treatment-emergent adverse events) (Part 2)

Primary Outcome 2 - Timeframe: whichever comes first

Primary Outcome 3 - Measure: Number of participants with DLTs (dose-limiting toxicities) (Part 1)

Primary Outcome 3 - 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

Primary Outcome 4 - Measure: Number of participants with DLTs (dose-limiting toxicities) (Part 2)

Primary Outcome 4 - Timeframe: whichever comes first

Primary Outcome 5 - Measure: Number of subjects with grade ≥3 TEAEs (Part 1)

Primary Outcome 5 - Timeframe: Up to day 28

Primary Outcome 6 - Measure: Number of subjects with grade ≥3 TEAEs (Part 2)

Primary Outcome 6 - Timeframe: Up to day 28

Primary Outcome 7 - Measure: Percentage of subjects with grade ≥3 TEAEs (Part 1)

Primary Outcome 7 - 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

Primary Outcome 8 - Measure: Percentage of subjects with grade ≥3 TEAEs (Part 2)

Primary Outcome 8 - Timeframe: whichever comes first

Primary Outcome 9 - Measure: Number of subjects with 1 or more SAEs (serious adverse events) (Part 1)

Primary Outcome 9 - 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

Primary Outcome 10 - Measure: Number of subjects with 1 or more SAEs (serious adverse events) (Part 2)

Primary Outcome 10 - Timeframe: whichever comes first

Primary Outcome 11 - Measure: Percentage of subjects with 1 or more SAEs (Part 1)

Primary Outcome 11 - 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

Primary Outcome 12 - Measure: Percentage of subjects with 1 or more SAEs (Part 2)

Primary Outcome 12 - Timeframe: whichever comes first

Primary Outcome 13 - Measure: Number of subjects with 1 or more TEAEs leading to dose modifications (Part 1)

Primary Outcome 13 - 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

Primary Outcome 14 - Measure: Number of subjects with 1 or more TEAEs leading to dose modifications (Part 2)

Primary Outcome 14 - Timeframe: whichever comes first

Primary Outcome 15 - Measure: Number of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 1)

Primary Outcome 15 - 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

Primary Outcome 16 - Measure: Number of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 2)

Primary Outcome 16 - Timeframe: whichever comes first

Primary Outcome 17 - Measure: Percentage of subjects with 1 or more TEAEs leading to dose modifications (Part 1)

Primary Outcome 17 - 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

Primary Outcome 18 - Measure: Percentage of subjects with 1 or more TEAEs leading to dose modifications (Part 2)

Primary Outcome 18 - Timeframe: whichever comes first

Primary Outcome 19 - Measure: Percentage of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 1)

Primary Outcome 19 - 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

Primary Outcome 20 - Measure: Percentage of subjects with 1 or more TEAEs leading to treatment discontinuation (Part 2)

Primary Outcome 20 - Timeframe: whichever comes first

CONDITION

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

ELIGIBILITY

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Ignacio Garcia-Ribas, MD, PhD

Role: Study Director

Affiliation: Cantargia AB

Overall Contact

Name: N/A

Phone: N/A

Email: N/A

LOCATION