ONC-392 Versus Docetaxel in Metastatic NSCLC That Progressed on PD-1/PD-L1 Inhibitors

This is a seamless 2-stage, randomized, open-label, active-controlled, Phase 3 study. The study population consists of patients with NSCLC who progressed on PD-1/PD-L1 inhibitor. Approximately 630 patients will be enrolled.

Two gotistobart dosing regimens will be tested in Stage I, and one will be selected for Stage II.

Stage I, the dose-confirmation stage, will assess the efficacy and safety of two gotistobart dosing regimens (3 mg/kg Q3W and 6 mg/kg Q3W with 2 loading doses of 10 mg/kg Q3W) in comparison to docetaxel 75 mg/m2 Q3W.

Stage II will assess the safety and efficacy of gotistobart at the selected dosing regimen versus docetaxel on squamous cell NSCLC. Patients will be randomized 1:1 to receive either gotistobart at the selected dosing regimen or docetaxel.

Inclusion criteria

(Major criteria):

• Adult (≥ 18 years), all genders, capable of signing informed consent.
• Histologically- or cytologically- confirmed diagnosis of metastatic squamous NSCLC, metastasis can be regional lymph nodes or distant organs.
• Radiographic progression after treatment with the most recent line of treatment being either 3a or 3b:

• At least 12 weeks of PD-1/PD-L1 inhibitor in combination with platinum-based chemotherapy;
• Prior treatment with at least 2 cycles of a platinum-based chemotherapy, followed by at least 12 weeks of standard doses of PD-1 or PD-L1 inhibitor-based immunotherapy.

Antibodies against CTLA-4, LAG-3, TIGIT, VEGF or VEGFR in combination with PD-1/PD-L1 inhibitor are allowed.

• At least one measurable tumor lesion according to RECIST 1.1.
• ECOG score of 0 or 1.
• Adequate organ functions. Serum LDH level ≤ 2xULN.
• Life expectancy ≥ 3 months.

Exclusion criteria

(Major criteria):

• Cancer treatment related AEs have not recovered to NCI CTCAE grade≤ 1 except endocrinopathy.
• Last anti-PD-1/PD-L1 dosing within 28 days prior to first dose of study treatment.
• Receiving systemic steroid therapy with >10 mg/day prednisone or equivalent within 7 days prior to the first dose of study treatment.
• Having documented actionable mutations or genomic alterations in any of the following genes: EGFR, ALK, ROS1, HER2, MET, BRAF, RET or NTRK;. Exception: KRAS mutations are not excluded.
• Patients who have symptomatic brain metastasis. Palliative radiotherapy or radiosurgery to brain metastasis within 14 days of the first dose of study drug.
• Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.
• Active interstitial lung disease (ILD) or non-infectious pneumonitis.
• Active infections with IV antibiotics within 14 days prior to first dose of study treatment.
• Impaired heart function.