662MO - Phase I, multi-center, dose-escalation and dose-expansion study of IMP7068, a WEE1 inhibitor, in patients with advanced solid tumors

Background

IMP7068 is a potent and highly selective WEE1 inhibitor. Ongoing phase 1 study showed preliminary antitumor activity with a manageable safety profile in patients (pts) with advanced solid tumors.

Methods

Eligible pts were enrolled in escalation cohorts starting with 30mg (administered orally, once [QD] or twice daily [BID] for 3 days, followed by 4 days off [3/4] every week for 21-day cycles).

Results

As of April 12, 2023, 50 pts were enrolled across 10 dose cohorts (Table). Additional schedules including 2 days of dosing followed by 5 days off (2/5) and 5 days of dosing followed by 2 days off (5/2) every week were suggested by SMC after the notice of grade 3 ECG QT prolongation. The most common (＞10%) treatment related adverse events were QT prolongation (28%), vomiting (16%), diarrhea (14%) and nausea (14%). 9 dose-limiting toxicities (DLTs) of grade 3 QT prolongation and pulmonary embolism were observed in 8 pts (Table). The mean QT interval prolongation in 80mg BID is lower than that in 160mg QD in schedule 3/4. 35 pts were efficacy evaluable, 1 patient with uterine serous cancer in cohort 4 has maintained complete response for 30 weeks, 18 pts had stable disease (SD), of which 1 patient with ovarian cancer in cohort 7 has maintained SD for 24 weeks. 5 pts are still on treatment. The pharmacokinetic (PK) analysis showed the exposure of IMP7068 in cohort 7 was comparable to that in cohort 4. The phosphorylated cyclin-dependent kinase 1 level in cohorts 4, 7 and 9 was reduced by ≥50% after treatment. Based on safety, PK and pharmacodynamic data, 80mg BID can be considered as a recommended phase 2 dose (PR2D) of 3/4 schedule. Table: 662MO

DLT by escalating cohorts

Conclusions

IMP7068 conferred promising antitumor activity and good tolerability as QT prolongation has been mitigated by altering schedule. 80mg was defined as a potential PR2D in 3/4 schedule, and a second potential RP2D is being explored in 5/2 schedule. RP2D for IMP7068 will be determined soon.

Clinical trial identification

NCT04768868.

Editorial acknowledgement

Legal entity responsible for the study

IMPACT Therapeutics, Inc.

Funding

IMPACT Therapeutics, Inc.

Disclosure

C. Lin: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Eli Lilly, Novartis, Roche; Financial Interests, Personal, Advisory Role: AbbVie, Bayer, Blueprint Medicines, Boehringer-Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Merck KGaA, Novartis, PharmaEngine, Rakuten; Financial Interests, Personal, Other, travel support: BeiGene, Eli Lilly, Impact. J.C. Baranda: Financial Interests, Institutional, Other, Consultant: Sanofi; Financial Interests, Personal, Stocks/Shares: Aprea, Moderna, Zyme, Merus, Hutchmed; Financial Interests, Institutional, Local PI: Astellas, Nektar, Sanofi, Takeda, Pfizer, SQZ, Synermore, Changchun Intellicrown, Genome and Company, Sumitomo Pharma, Xencor. D. Sommerhalder: Financial Interests, Personal, Other, Ad-hoc advisory role: Syneos SAG; Financial Interests, Personal, Other, Medical consulting: Guidepoint; Financial Interests, Institutional, Full or part-time Employment, Employed as a physician by Texas Oncology, a for-profit entity: Texas Oncology/US Oncology; Financial Interests, Institutional, Local PI: Astellas, Biomea Fusion, Boehringer Ingelheim, BJ Biosciences, BioNTech, Fate Therapeutics, Gilead Sciences, Immuneering, Kura Oncology, Monopteros Therapeutics, Navire, Nimbus Saturn, NGM Biopharmaceuticals, Parthenon, Pfizer, Revolution Medicines, Mirati Therapeutics, Symphogen, Teon Therapeutics, MediLink Therapeutics, ZielBio. L. Shen: Financial Interests, Personal, Other, Consulting fees: Mingji biopharmaceutical, Haichuang pharmaceutical, Herbour biomed; Financial Interests, Personal, Advisory Board: MSD, Merck, BMS, BI, Sanofi, Roche, Servier, AZ; Financial Interests, Institutional, Funding: Beijing Xiantong Biomedical Technology, Qilu Pharmaceutical, ZaiLab Pharmaceutical (Shanghai), Alphamab Oncology, Yaojie Ankang (Nanjing) Technology Co., Ltd., BeiGene, Ltd., Qiyu Biotechnology (Shanghai) Co., Ltd., BriSTAR immunotech; Financial Interests, Institutional, Local PI: Merck Healthcare KGaA, Roche; Financial Interests, Institutional, Trial Chair: Rongchang Pharmaceutical, Innovent, BeiGene, Ltd., Qilu Pharmaceutical, NovaRock Biotherapeutics Limited. O. Alese: Other, Institutional, Research Grant: Taiho Oncology, Ipsen Pharmaceuticals, GSK, Bristol Myers Squibb, PCI Biotech AS, ASCO, Calithera Biosciences, Inc., SynCore Biotechnology Co. Ltd., Suzhou Transcenta Therapeutics Co., Ltd., Corcept Therapeutics Inc., Hutchison MediPharma, Boehringer Ingelheim, Xencor Inc., Cue Biopharma, Inc., Merck, Syros Pharmaceuticals Inc., Inhibitex Inc., Arcus Biosciences Inc., ImmunoGen; Other, Personal, Advisory Role: Ipsen Pharmaceuticals, Aadi Bioscience, Taiho, Pfizer, Seagen Inc., Bristol Myers Squibb, AstraZeneca. All other authors have declared no conflicts of interest.