NIPH Clinical Trials Search

A study to compare setidegrasib (ASP3082) with docetaxel, in people with non-small cell lung cancer with a KRAS G12D mutation

Basic Information

Recruitment status	Pending
Health condition(s) or Problem(s) studied	Non-small cell lung cancer (NSCLC)
Date of first enrollment	29/05/2026
Target sample size	356
Countries of recruitment	United States,Japan
Study type	Interventional
Intervention(s)	In this study, people will either receive setidegrasib or docetaxel. Whether people receive setidegrasib or docetaxel is decided by chance, not by the study doctor. Both study treatments are given slowly through a tube into a vein (infusion). People will continue to receive study treatment until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatment, they or the doctor decides the person should stop receiving study treatment, or sadly, they pass away. Some people on docetaxel may be able to switch to setidegrasib during the study if their cancer becomes worse. There will be safety checks at each visit, and the doctors will continue to check for medical problems and people's wellbeing throughout the study. People will continue to have scans of their tumor every 6 weeks for the first year, then every 9 weeks until their cancer becomes worse. After people's cancer becomes worse, clinic staff will telephone people every 12 weeks to check on their cancer.

Outcome(s)

Primary Outcome

- Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as assessed by blinded independent central review (BICR) - Overall survival (OS), defined as the time from the date of randomization until the date of death from any cause

Secondary Outcome

- Time to deterioration in NSCLC symptoms (TDLCS), evaluated via European Organisation for Research and Treatment of Cancer Lung Cancer Module (EORTC QLQ-LC13) items 31 (coughing), 33 to 35 (dyspnea) and 40 (chest pain) - Time to worsening in global health status (GHS)/ quality of life (QoL) (TWGQ), evaluated via European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) items 29 and 30 - Objective response rate (ORR) per RECIST v1.1, as assessed by BICR - Time to response (TTR), duration of response (DOR) and disease control rate (DCR) per RECIST v1.1, as assessed by BICR; PFS, ORR, TTR, DOR and DCR per RECIST v1.1, as assessed by the investigator - Safety and tolerability evaluated via the following: adverse events (AEs), serious adverse events (SAEs), laboratory test results, electrocardiograms (ECGs), vital signs, ECOG PS and assessment of harm, as measured by OS - End of infusion (EOI ) concentration and observed trough concentration (Ctrough) - Change from baseline until week 12 in EORTC QLQ-C30, EORTC QLQ-LC13, EuroQol 5-dimensional 5-level version (EQ-5D-5L) visual analogue scale (VAS), Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) - Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and Functional Assessment of Cancer Therapy - General Item 5 (FACT-GP5) responses over time

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include criteria	1. Participant has histologically confirmed locally advanced (unresectable) or metastatic NSCLC with documented KRAS G12D mutation result status, based on local or central testing. - The participant's positive KRAS G12D mutation result (either in tumor tissue or plasma circulating tumor DNA [ctDNA]) must be available prior to randomization. - If the participant is enrolling based on a local testing result, the result may have been based on tissue or liquid (blood) testing. If the participant is enrolling via central testing, the eligibility sample must be from tissue. 2. Participant must have progressed or experienced disease recurrence on or after platinum based chemotherapy (which includes but is not limited to platinum combinations with pemetrexed, paclitaxel, etoposide or gemcitabine) in combination with anti-programmed cell death 1 (PD-1)/PD-L1 antibody OR platinum-based chemotherapy and anti-PD-1/PD-L1 antibody (in either order) sequentially in the locally advanced (unresectable) or metastatic setting (participant who received anti PD-1/anti-PD-L1 antibody or platinum-based chemotherapy as first-line therapy in the locally advanced [unresectable] or metastatic setting may have received the combination of platinum-based chemotherapy and anti PD1/anti PD L1 antibody in the second line locally advanced [unresectable] or metastatic setting). - No additional treatments are allowed in the locally advanced (unresectable) or metastatic setting, with the exception of: o Anti-vascular endothelial growth factor (VEGF) therapy (e.g., bevacizumab), when administered in combination with platinum-based chemotherapy and/or anti-PD-1/PD-L1 as part of a first-line standard regimen in the locally advanced (unresectable) or metastatic setting and o Anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies (e.g., ipilimumab, tremelimumab), when administered in combination with anti-PD-1/PD-L1 (with or without platinum-based chemotherapy) as part of a first-line standard regimen in the locally advanced (unresectable) or metastatic setting. - For the purposes of eligibility, for a participant who has received prior neoadjuvant or adjuvant therapy and has had recurrence during or within 6 months of completion of therapy, the neoadjuvant or adjuvant therapy will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting (for those who received perioperative therapy, the entire course will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting). - For the purposes of eligibility, for a participant with a history of unresectable Stage III disease who has received prior multi-modal therapy and has had recurrence on or within 6 months of completion of therapy, the multi-modal therapy will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting. If chemoradiation was followed by treatment with CPI without documented progression between chemoradiation and CPI, the entire treatment course will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting, for the purposes of eligibility. - Maintenance therapy following platinum doublet-based chemotherapy is not considered a separate line of therapy. 3. Female participant: - is not pregnant and at least 1 of the following conditions apply: a. Not a woman of childbearing potential (WOCBP). b. WOCBP must have a negative serum pregnancy test at screening with a medical interview and agrees to follow the contraceptive guidance from the time of informed consent through >/= 6 months after the final setidegrasib administration or >/= 2 months after the final docetaxel administration, as applicable. - Must not be breastfeeding or lactating starting at screening and throughout the investigational period and for >/= 6 months after the final setidegrasib administration or >/= 2 months after the final docetaxel administration, as applicable. (Note that this is stricter than some docetaxel product information/labeling documents due to the uncertainty regarding excretion of docetaxel in human milk.) - Must not donate ova starting at first administration of study intervention and throughout the investigational period and for >/= 6 months after the final setidegrasib administration or >/= 2 months after the final docetaxel administration, as applicable. 4. Participant consents to and provides a baseline tumor tissue and plasma specimen during prescreening and/or screening. 5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to randomization.
Exclude criteria	1. Participant has known untreated or symptomatic central nervous system (CNS) metastases. Participant with previously treated brain metastases may be eligible if they have stable CNS disease for >/= 2 weeks prior to randomization, all neurologic symptoms have returned to baseline, there is no evidence of new or enlarging brain metastases on brain imaging performed within 28 days prior to randomization and they are receiving </= 10 mg/day of prednisone or equivalent. 2. Participant has mixed small-cell lung cancer and NSCLC histology. 3. Participant has leptomeningeal disease as a manifestation of the current malignancy. 4. Participant has another prior malignancy active (i.e., requiring treatment, including hormonal therapies, or intervention) within the previous 2 years different from the primary malignancy for this study, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed. 5. Participant has known active hepatitis B virus (HBV) (defined as hepatitis B surface antigen [HBsAg]-positive or anti HBV core antibody-positive) or known active hepatitis C virus (HCV) (defined as HCV ribonucleic acid [RNA] [qualitative] detected) infection. 6. Participant with human immunodeficiency virus (HIV) infection may be eligible if the participant has not had an opportunistic infection within the past 12 months. Participant must be on established antiretroviral therapy for >/= 4 weeks, have a CD4+ T cell >/= 200 cells/microliter and must have an HIV viral load < 400 copies/mL prior to randomization. 7. Participant has current grade >/= 2 peripheral neuropathy. 8. Participant has uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Participant with PleurX catheters in place may be considered for the study with medical monitor approval. 9. Participant has received therapeutic or palliative radiation therapy within 14 days prior to randomization (see first Exclusion Criterion for CNS metastases); participant must have recovered from all radiotherapy related toxicity to </= grade 1, with the exception of alopecia [any grade of alopecia allowed]). 10. Participant has a known actionable mutation for which an approved targeted therapy is locally available, including, but not limited to, KRAS G12C mutation, epidermal growth factor receptor (EGFR) mutation (exon 19 deletions, exon 21 L858R point mutation, T790M, exon 20 insertion), anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearrangement, neurotrophic tyrosine receptor kinase (NTRK) fusion, neuregulin 1 (NRG1) fusion, B-Raf proto-oncogene (BRAF) V600E mutation, mesenchymal-epithelial transition (MET) exon 14 skipping mutation, rearranged during transfection (RET) rearrangement or human epidermal growth factor receptor 2 (HER2) activating mutation. 11. Participant has received prior treatment with either docetaxel or a KRAS-targeting agent (including KRAS directed inhibitors, degraders, small interfering RNA[siRNA], vaccines and cellular therapies). 12. Participant requires treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450 (CYP)3A or CYP2D6.