Phase 1 Study of BPI-442096 in Advanced Solid Tumor Patients

Betta Pharmaceuticals

Status and phase: Not yet enrolling; Phase 1

Conditions: Solid Tumor; Non-small Cell Lung Cancer; Colorectal Cancer; Pancreatic Cancer

Treatments: Drug: BPI-442096

Study type: Interventional

Funder types: Industry

Identifiers

NCT05369312

BTP-661711

Details and patient eligibility

About

A first-in-human study to evaluate the safety, tolerability and maximum tolerated dose (MTD) and establish the recommended phase 2 dose (RP2D) of BPI-442096, a SHP2 inhibitor, in patients with advanced solid tumors.

Full description

The first-in-human (FIH) study of BPI-442096 will be an open-label, non-randomized, Phase 1 study utilizing a modified "3+3" dose escalation followed by an expansion phase in patients with KRAS G12 mutation, class-3 BRAF mutation, NF1 LOF mutation or RTK mutation, amplification or rearrangement advanced solid tumors. The primary objective is to determine safety and tolerability of BPI-442096, the MTD and RP2D. The secondary objectives are to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profile, preliminary anti-tumor activity of BPI-442096.

Enrollment: 230 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed informed consent;
• Age ≥18 and ≤75 years, male and female patients;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1;
• Dose escalation phase: histologically or cytologically confirmed locally advanced or metastatic solid tumor patients (excluding HCC patients), who had disease progression after standard therapy, intolerable to standard therapy, refuse to standard therapy or for whom no standard therapy exists;
• Dose expansion phase: histologically or cytologically confirmed locally advanced non-small cell lung cancer, pancreatic cancer, colorectal cancer or other diagnosed solid tumor patients (excluding HCC patients), who had disease progression after standard therapy, intolerable to standard therapy, refuse to standard therapy or for whom no standard therapy exists;
• Evaluable lesion required for dose escalation phase and at least 1 measurable lesion as per RECIST v1.1 required for dose expansion phase;
• Dose expansion only: Patients must have confirmation of tumour mutation status (including KRAS G12, Class-3 BRAF, NF1 LOF mutations, RTK mutations, amplifications or rearrangements).
• Adequate organ function;

Exclusion criteria

• Patients who have previously received a SHP2 inhibitor;
• Inadequate wash-out of prior therapies described per protocol, which may include anti-tumor therapies, tumor adjuvant drugs, organ or stem cell transplantation, moderate or strong CYP3A inhibitor or inducer;
• Patients with severe or unstable systemic disease, unstable/symptomatic CNS metastasis, other malignant tumors, autoimmune disease, ILD, cardiac disease, bleeding or embolic disease, infectious disease, conditions affecting drug swallow and absorption, medical history leading to chronic diarrhea, etc;
• Pregnancy or lactation;
• Other conditions considered not appropriate to participate in this trial by the investigators.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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230 participants in 2 patient groups

Dose Escalation

Experimental group

Description:

Oral tablets taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 21 days in duration with BPI-442096 administered, once daily (QD).

Treatment:

Drug: BPI-442096

Dose Expansion

Experimental group

Description:

Oral tablets administered at MTD/RP2D defined dose. Each treatment cycle will be 21 days in duration with BPI-442096 administered, once daily (QD)

Treatment:

Drug: BPI-442096