A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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To evaluate the safety, tolerability, and DLTs and determine the MTD and/or RDE(s) of INCA33890 in participants with select advanced or metastatic solid tumors.

Official Title
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A Phase 1, Open-Label, Multicenter Study of INCA33890 in Participants With Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumors, Advanced Solid Tumors, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: INCA33890


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old Histologically or cytologically confirmed advanced or metastatic malignancies Participants must have experienced disease progression after treatment with available therapies, including anti-PD-(L)1 or anti-CTLA4 therapy if applicable, that are known to confer clinical benefit, or who are intolerant to, or ineligible for standard treatment. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance. ECOG performance status score of 0 or 1. Willingness to undergo pre- and on-treatment tumor biopsy (core or excisional) Presence of measurable disease according to RECIST v1.1 Part 1a only: Participants who have been previously treated with PD-1 inhibitor must undergo a washout period of 5 months or 5 times the half-life of the last PD-1, whichever is shorter, before the first dose of study drug. Bladder cancer (BC): Mixed histology with predominant urothelial carcinoma component is allowed. Pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded. Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) Esophageal cancer (ESCA) Gastric adenocarcinoma (GC) Gastroesophageal adenocarcinoma (GEJ) Cutaneous malignant melanoma (Mel) Malignant pleural mesothelioma (MPM) Non-small cell lung cancer (NSCLC): Either squamous or nonsquamous histology is allowed. For mixed histology, there must be a predominant histology. Mixed small cell and non-small cell lung cancer histology is excluded. Tumors should not exhibit mutations in EGFR, ALK, ROS1, or BRAF. Ovarian Cancer (OC): Epithelial ovarian, fallopian tube, primary peritoneal carcinoma, or carcinosarcoma Sertoli-Leydig or germ cell cancers are excluded. Renal cell carcinoma (RCC) Head and neck squamous cell carcinoma (SCCHN): histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy) Carcinoma of the nasopharynx, salivary gland, or nonsquamous histologies are excluded. Triple-negative breast cancer (TNBC): HER2-negative, ER-negative, and PgR-negative Pancreatic adenocarcinoma (PAAD) Colorectal cancer (CRC) Exclusion Criteria: Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years Not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy Has active autoimmune disease requiring systemic immunosuppression with corticosteroids Brain or CNS metastases untreated or that have progressed . History of organ transplant, including allogeneic stem cell transplantation. Received more than 4 prior anticancer regimen(s) for advanced or metastatic disease. History of clinically significant or uncontrolled cardiac disease Active HBV (or at risk of activation), active HCV, or HIV positive Is on chronic systemic steroids (> 10 mg/day of prednisone or equivalent). Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment Participants that have been initiated on or had modifications in anticoagulation therapies within the last 3 months prior to first dose of treatment. Significant concurrent, uncontrolled medical condition, eg: Cardiovascular: Participants with known vasculitis, aneurisms, and other vascular malformations of clinical significance Participants with adequate laboratory values within the protocol defined ranges.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1a - Dose Escalation<br>INCA33890 will be administered at a protocol defined starting regimen intravenously. Subsequent dose regimens will be determined during study conduct. | Drug: INCA33890<br>* INCA33890 will be administered at protocol defined dose.<br>|
| Experimental: Part 1b-Dose Expansion<br>INCA33890 will be administered at the recommended dose(s) for expansion (RDE[s]) in participants with advanced or metastatic ICI sensitive or ICI non sensitive tumor types | Drug: INCA33890<br>* INCA33890 will be administered at protocol defined dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Dose Limiting Toxicities (DLTs) |  | Up to 28 days | 
| Number of participants with Treatment Emerging Adverse Events (TEAEs) |  | Up to 2 years | 
| Number of participants with TEAEs leading to dose modification or discontinuation |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response Rate |  | 2 years | 
| Disease Control Rate |  | 2 years | 
| Duration of Response |  | 2 years | 
| Pharmacokinetics Parameter : Cmax of INCA33890 |  | Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up | 
| Pharmacokinetics Parameter : Tmax of INCA33890 |  | Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up | 
| Pharmacokinetics Parameter : Cmin of INCA33890 |  | Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up | 
| Pharmacokinetics Parameter : AUC(0-t) of INCA33890 |  | Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up | 
| Pharmacokinetics Parameter : AUC 0-∞ of INCA33890 |  | Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up | 
| Pharmacokinetics Parameter : CL/F of INCA33890 |  | Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up | 
| Pharmacokinetics Parameter : Vz/F of INCA33890 |  | Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up | 
| Pharmacokinetics Parameter : t1/2 of INCA33890 |  | Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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INCA33890, Solid Tumors