A Study to Investigate the Safety and Efficacy of KQB198 as Monotherapy and in Combination in Participants With Advanced Solid Malignancies

A Phase 1/1b, Open-label, Multicenter, Dose Escalation and Dose Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of KQB198 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies

The goal of this clinical trial is to learn if KQB198 works to treat advanced solid tumor cancer in adults. It will also learn about the safety of KQB198. The main questions it aims to answer are:

• What is the safe dose of KQB198 by itself or in combination with other anti-cancer drugs?
• Does KQB198 alone or in combination with other anti-cancer drugs decrease the size of the tumor?
• What happens to KQB198 in the body?

Participants will:

• Take KQB198 daily, alone or in combination with another anti-cancer drug
• Visit the clinic about 8 times in the first 8 weeks, and then once every 4 weeks after that

Inclusion Criteria:

• PART 1 - Histologically confirmed diagnosis of a solid tumor malignancy with any of the following oncogenic mutations: EGFR, RAS, PTPN11, or SOS1 mutations, or inactivating mutations of NF1.
• PART 1 - (Osimertinib and Amivantamab arms) and Part 2 Cohort A and Cohort B: Histologically confirmed diagnosis of NSCLC with activating EGFR mutation and progression on osimertinib
• Part 3 - Cohort A: Histologically confirmed diagnosis of NSCLC with exon 20 insertion EGFR mutation
• Unresectable or metastatic disease
• No available treatment with curative intent
• Adequate organ function
• Measurable disease per RECIST 1.1.

Exclusion Criteria:

• Prior therapy with a similar mechanism of action to KQB198
• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
• History of interstitial lung disease
• Cardiac abnormalities