Study Assessing MTD, Safety, Tolerability, PK and Anti-tumor Effects of LNS8801alone and With Pembrolizumab

Solid Tumor, Adult Clinical Trial

Official title: A Multicenter Phase 1-2A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of LNS8801 in Patients With Advanced Cancer With and Without Pembrolizumab

Status Recruiting

Clinical Trial Summary

This Phase 1/2, first-in-human, open-label, multicenter study follows a 3+3 ascending dose escalation design to determine the MTD/RP2D and to characterize the safety, tolerability, PK, and antitumor effects of LNS8801 alone and in combination with pembrolizumab. The study will include a dose escalation phase, a dose expansion phase, and phase 2A cohorts. Up to 200 patients will be accrued for this study. Up to 15 study sites in the United States will participate in the study.

Clinical Trial Description

In this Phase 1/2, first-in-human, open-label, multi-center study. Dose escalation cohorts enrolled at least 3 patients in accordance with a traditional dose escalation 3+3 design, and the study will determine the MTD/RP2D of LNS8801. LNS8801 will be administered orally 3 days/week or once or twice a day during 21 day cycles until disease progression or unacceptable toxicity occurs. Safety assessments will be performed on all patients at screening, throughout their participation in the study, and for 30 days (90 days in combination cohorts) following the last dose of study drug. Throughout the study, imaging of tumors for evidence of tumor response and/or progression will be performed; biopsies will be performed on accessible lesions. After the RP2D of LNS8801 is identified and the safety of dosing LNS8801 with pembrolizumab has been established, expansion cohorts and Phase 2A cohorts will open. Any 2 dose escalation cohorts may be expanded to 8 to 10 patients to include additional patients to further explore PK and PD. Phase 1B expansion cohorts include a monotherapy cohort (LNS8801 alone) of melanoma patients (not uveal) who are now not eligible for additional anti-PD-1 therapy in the judgement of the investigator because of prior severe immune related adverse events and a combination therapy (LNS8801 + pembrolizumab) cohort in anti-PD-1/L1 refractory advanced cancer patients who have previously had clinical benefit on anti-PD-1/L1 therapy alone or in combination (complete response or partial response of any duration, or confirmed stable disease for at least 16 weeks) but have since relapsed and not had an intervening cytotoxic chemotherapy. Up to 28 evaluable patients may be studied in each cohort. The study will also include the following 8 Phase 2A cohorts. Monotherapy with 125 mg LNS8801 PO: COHORT M2: 20 evaluable patients with no remaining SOC therapies with pancreatic, gastric, non small cell lung cancer (NSCLC) or colorectal cancers. COHORT M3: 10 evaluable patients with no remaining SOC therapies with advanced malignant cutaneous melanoma having received as their immediate prior line of therapy a PD-1/L1 targeted immune checkpoint inhibitor (IO), alone or in combination, and who are now not eligible for anti-PD-1 treatment in the judgement of the Investigator due to prior severe immune related adverse events. COHORT M4: 10 patients with advanced solid tumor malignancies and no remaining SOC therapies, other than cutaneous melanoma, having received as their immediate prior line of therapy a PD-1/L1 targeted immune checkpoint inhibitor (IO), alone or in combination, and having been forced to discontinue IO therapy due to an immune-related adverse event (irAE). COHORT M5: 10 evaluable patients with metastatic uveal melanoma and no remaining SOC therapies that have 2 or fewer prior lines of systemic therapy. Combination therapy cohorts treated with 125 mg LNS8801 daily PO + 200 mg Q3W Pembrolizumab IV: COHORT C2: 20 evaluable patients with no remaining SOC therapies with pancreatic, gastric, non small cell lung cancer (NSCLC) or colorectal cancers. COHORT C3: 10 evaluable patients with metastatic non-small cell lung cancer (NSCLC) expressing PD-L1 (Tumor Proportion Score [TPS] ≥1% and ≤49%) as determined by an FDA-approved test will be treated with the combination of LNS8801 plus pembrolizumab. Eligible patients must either have no EGFR or ALK genomic tumor aberrations or have not demonstrated disease response on or following FDA-approved therapy for these aberrations. Inclusion and exclusion criteria will otherwise be consistent with those criteria specified above. COHORT C5: 10 evaluable patients with metastatic uveal melanoma and no remaining SOC therapies that have 2 or fewer prior lines of systemic therapy. COHORT C6: 10 evaluable patients with advanced malignant cutaneous melanoma and no remaining SOC therapies. Up to 200 patients will be accrued for this study at up to 15 study sites in the United States. ;

Related Conditions & MeSH terms

• Solid Tumor, Adult

• NCT number: NCT04130516
• Study type: Interventional
• Source: Linnaeus Therapeutics, Inc.
• Contact: Tina Garyantes, PhD
• Phone: (908) 420-1159
• Email: tgaryantes@linnaeustx.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 21, 2019
• Completion date: December 15, 2024