Ipatasertib combined with docetaxel for advanced lung cancer patients after failed immunotherapy

A Multi-center Phase II Study of Ipatasertib in Combination With Docetaxel in Metastatic/Advanced NSCLC Patients Who Have Failed or Are Intolerant to 1st Line Immunotherapy (Ipat-Lung)

This study is testing if a new combination of ipatasertib and docetaxel can help advanced lung cancer patients who didn't respond to previous immunotherapy treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Kansas Medical Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 5 sites (Fairway, Kansas and 4 other locations)
• Trial ID: NCT04467801 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of ipatasertib, an ATP-competitive inhibitor, in combination with docetaxel for patients with metastatic non-small cell lung cancer (NSCLC) who have not responded to first-line immunotherapy. The study aims to provide a novel treatment option for patients who have either failed or are intolerant to standard therapies. By targeting the AKT pathway, the trial seeks to enhance the therapeutic effects of chemotherapy and potentially improve patient outcomes. Participants must have measurable disease and meet specific eligibility criteria, including a life expectancy of at least 12 weeks.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced metastatic NSCLC who have failed or are intolerant to first-line anti-PD1/PD-L1 therapies.

Not a fit: Patients with targetable mutations or those who have not yet received first-line immunotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced NSCLC who have limited treatment alternatives.

How similar studies have performed: Other studies have shown promising results with similar approaches targeting the AKT pathway in combination with chemotherapy, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

* Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
* Life expectancy ≥12 weeks
* Males and females age ≥ 18 years
* Allowable type and amount of prior therapy:

First line anti-Programmed death receptor and ligand (PD1/PD-L1), either single agent or in combination with chemotherapy

* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Measurable disease per RECIST version 1.1
* Diagnoses of advanced/metastatic NSCLC and have failed or are intolerant to 1st line anti-PD1/PD-L1, either single agent or in combination with chemotherapy, and have either exhausted or decline or not be candidates for all available standard of care therapies.
* Adequate organ function
* Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use an acceptable form of contraception for the duration of study participation, and for 90 days following completion of therapy
* Men of child-bearing potential must agree not to donate sperm while on this study and for 90 days after their last study treatment

Exclusion Criteria:

* Is not concurrent enrolled in another clinical study, unless it is an observational (non-interventional) clinical study or if the participant is in the follow-up period of an interventional study
* Is not currently on or is not anticipated to use other investigational agents within 14 days prior to and while participating in this study
* Does not have mixed small cell and non-small cell lung cancer histology
* Does not have any unresolved toxicity CTCAE \>Grade 2 from the prior 1st immunotherapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included
* Patients who have targetable mutations that qualify for targeted therapy (e.g. mutations of epidermal growth factor receptor (EGFR), serine/ threonine- protein kinase (BRAF), anaplastic lymphoma kinase (ALK), tyrosine- protein kinase (ROS1), neurotrophic receptor tyrosine kinase (NTRAK)) will be excluded from this study
* Is not on concomitant therapy intended for the treatment of cancer (including, but not limited to, chemotherapy, hormonal therapy, immunotherapy, radiotherapy, and herbal therapy) for 14 days prior to starting study treatment, depending on the agent and during study treatment, until disease progression is documented and the patient has discontinued study treatment, with the exception of palliative radiotherapy and local therapy per PI discretion
* Does not chronically use a strong cytochrome P4503A4 (CYP3A4/5) inhibitor or inducer, or sensitive CYP3A substrates with a narrow therapeutic window
* Has not had recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug
* Does not have uncontrolled systemic disease
* Does not have uncontrolled brain metastasis
* Does not have history of allergy to taxanes
* Does not have history of leptomeningeal carcinomatosis
* Does not have recent history of myocardial infarction (MI) or symptomatic coronary artery disease within 6 months of screening
* Is not receiving active therapy for HIV, hepatitis B or hepatitis C
* Does not have history of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
* Does not have history of Type I or Type II diabetes mellitus requiring insulin (Patients who are on a stable dose of oral diabetes medication greater than or equal to 2 weeks prior to initiation of study treatment
* Does not have Grade greater than or equal to 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
* Does not have history of or active inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)
* Does not have active pneumonitis
* Does not have history of lung disease: interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections
* Does not have uncontrolled pleural effusion/pericardial effusion/or ascites as determined by the investigator
* Does not have active ventricular arrhythmia requiring medication
* Does not have psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent
* Is not pregnant, breast feeding or planning to become pregnant while receiving study treatment or for less than 90 days after the last dose of study treatment
* For males with partners of childbearing potential, is not planning to father a child or donate sperm while receiving study treatment or for less than 90 days after the last dose of study treatment
* Does not have any condition that, in the opinion of the investigator, would interfere with evaluation or interpretation of patient safety or study results

Where this trial is running

Fairway, Kansas and 4 other locations

• The University of Kansas Cancer Center (KUCC) — Fairway, Kansas, United States (Recruiting)
• The University of Kansas Cancer Center, Westwood Campus — Kansas City, Kansas, United States (Recruiting)
• The University of Kansas Cancer Center, Overland Park Clinic — Overland Park, Kansas, United States (Active_not_recruiting)
• The University of Kansas Cancer Center, North Clinic — Kansas City, Missouri, United States (Active_not_recruiting)
• The University of Kansas Cancer Center, Lee's Summit Clinic — Lee's Summit, Missouri, United States (Active_not_recruiting)

Study contacts

• Principal investigator: Jun Zhang, MD, PhD — The University of Kansas
• Study coordinator: KUCC Navigator

Conditions NSCLC Stage IV; NSCLC Stage IIIB; Advanced/metastatic NSCLC