Sapanisertib and Nivolumab for the Treatment of Stage I-IV Non-small Cell Lung Cancer in Patients Who Have Progressed on Prior PD-1/PD-L1 Inhibitor Therapy, I-OVERCOME Study

NCT05022394 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 2019-1262NCI-2020-02356
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I/II trial studies the side effects of sapanisertib and nivolumab and to see how well they work in treating patients with stage I-IV non-small cell lung cancer whose disease got worse on previous PD-1/PD-L1 inhibitor therapy. Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sapanisertib and nivolumab may help to control the disease.

Conditions

Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage I Lung Cancer AJCC v8; Stage II Lung Cancer AJCC v8; Stage IIA Lung Cancer AJCC v8; Stage IIB Lung Cancer AJCC v8; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Objective response rate (ORR)

  Will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Objective response rate will be calculated as the number of responders divided by the number of evaluable patients along with a 90% confidence interval. The ORR by dose level will also be evaluated.

  Cycle 1 through Cycle 4 (each cycle is 28 days)

• Incidence of dose limiting toxicity (DLT)

  Dose Limiting Toxicity will be measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Toxicity data will be tabulated using frequency and percentage by type, grade, and attribution.

  Cycle 1 through Cycle 4 (each cycle is 28 days)

Secondary Outcomes (5)

• Progression-free survival (PFS)

  From enrollment until progression or death, assessed up to 16 months

• Overall survival (OS)

  From enrollment until death by any cause, assessed up to 16 months

• Disease control rate

  Cycle 1 through Cycle 4 (each cycle is 28 days)

• Maximum serum concentration of sapanisertib (Cmax)

  Up to 16 months

• Area under the plasma drug concentration-time curve (AUC)

  Up to 16 months

Study Arms (1)

Treatment (sapanisertib, nivolumab)

EXPERIMENTAL

Patients receive PO QD on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab; Drug: Sapanisertib

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (sapanisertib, nivolumab)

Sapanisertib DRUG

Given PO

Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228

Treatment (sapanisertib, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with stage IV non-small cell lung cancer with disease progression on or up to 6 months from treatment with PD-1/PD- L1 inhibitor either alone or in combination with chemotherapy and/or anti-CTLA4 inhibitor; or patients with stage I-III non-small cell lung cancer with disease recurrence up to 6 months from receiving neoadjuvant/adjuvant/consolidation PD-1/PD-L1 inhibitor
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• All immune-related adverse events (AEs) while receiving prior immunotherapy must have resolved to grade =\< 1 prior to screening for the study. Patients with endocrine immune-related AE of =\< grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are women of childbearing potential (WOCBP), agree to practice 1 effective method of contraception and 1 additional effective (barrier) method, at the same time, and must agree to follow instructions for methods of contraception from the time of signing the informed consent, for the duration of treatment with nivolumab and 5 months after the last dose of nivolumab (ie 30 days \[duration of ovulatory cycle\] plus the time required for nivolumab to undergo approximately five half-lives), OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
• Agree not to donate egg(s) during the course of this study or within 5 months after the last dose of nivolumab (ie 30 days \[duration of ovulatory cycle\] plus the time required for nivolumab to undergo approximately five half-lives)
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
• Are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with nivolumab and up to 7 months after the last dose of nivolumab (ie 90 days \[duration of sperm turnover\] plus the time required for nivolumab to undergo approximately five half-lives)., OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together)
• Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L without transfusion within 1 week preceding study drug administration

You may not qualify if:

• Histology other than non-small cell lung cancer
• Central nervous system (CNS) metastasis that is symptomatic and uncontrolled
• Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• Presence of an EGFR, ALK, and ROS1 alteration
• Current systemic anti-cancer treatment other than the study agents, including other investigational agents
• Previous toxicity that led to permanent and indefinite discontinuation of prior immunotherapy
• Toxicity from prior immunotherapy required the use of additional immunosuppression other than corticosteroids for management of the AE
• Experienced recurrence of grade \>= 3 immune-related AE if re-challenged with immunotherapy. Patients with endocrine immune-related AE of =\< grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Known human immunodeficiency virus infection
• Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Concurrent malignancy with evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Breast feeding or pregnant women
• Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Nivolumab; sapanisertib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marcelo V Negrao, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: August 26, 2021
• Study Start: February 18, 2021
• Primary Completion: February 18, 2021
• Study Completion: February 18, 2021
• Last Updated: May 27, 2022

Record last verified: 2022-05