Treatment for Advanced Non-small Cell Lung Cancer With Actionable Genomic Alterations After Targeted Treatment and Chemotherapy (An Expanded Lung-MAP Treatment Trial)

NCT07393555 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: S1900NNCI-2026-00250U10CA180888
• Study Type: interventional
• Target: 117
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II Expanded Lung-MAP treatment trial compares how well sacituzumab govitecan alone, ivonescimab alone, or sacituzumab govitecan in combination with ivonescimab works in treating patients with non-small cell lung cancer (NSCLC) that has come back after a period of improvement (recurrent) or is stage IV and has a change in at least 1 of these genes: ALK, EGFR, HER2 (ERBB2), MET, NTRK, RET, and ROS1. This type of gene change is called an actionable genomic alteration (AGA), which means certain treatments can target the change to fight the cancer. Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a toxic drug called SN-38. Sacituzumab govitecan is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as TROP2 receptors, and delivers SN-38 to kill them. Ivonescimab is a bispecific antibody that can bind to two different antigens at the same time. It binds to programmed cell death protein 1 (PD1), a protein found on the surface of T cells (a type of white blood cell) and vascular endothelial growth factor (VEGF), a protein found on the surface of tumor cells. Ivonescimab may strengthen the immune system and interfere with the ability of tumor cells to grow and spread. Giving a combination of sacituzumab govitecan and ivonescimab work better than either drug alone, and sacituzumab govitecan alone, ivonescimab alone, or sacituzumab govitecan and ivonescimab together may work better than standard treatments at shrinking NSCLC with an AGA.

Conditions

Stage IV Lung Cancer AJCC v8; Recurrent Lung Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (5)

• Progression-free survival (PFS) (Comparison between arms)

  Will compare between participants randomized to the combination of sacituzumab govitecan plus ivonescimab (SG-I) and sacituzumab govitecan (SG) alone. The comparison of PFS will be done using a 1-sided 10% level log-rank test stratified by randomization stratification factors. Binary proportions along with 90% confidence intervals will be estimated for response to be consistent with 1-sided 5% level testing. With 35 participants per arm, binary proportions can be estimated to within 11% with 90% confidence. The distribution PFS will be estimated using the method of Kaplan-Meier. Comparisons of event time distributions between arms will be summarized by hazard ratios and 80% confidence intervals (consistent with 1-sided 10% level testing) from a Cox Proportional hazards model including the stratification factors.

  From date of randomization to date of first documentation of progression, symptomatic deterioration, or death due to any cause, assessed up to 3 years

• PFS (Comparison between arms)

  Will between participants randomized to SG-I and ivonescimab (I) alone. The comparison of PFS will be done using a 1-sided 10% level log-rank test stratified by randomization stratification factors. Binary proportions along with 90% confidence intervals will be estimated for response to be consistent with 1-sided 5% level testing. With 35 participants per arm, binary proportions can be estimated to within 11% with 90% confidence. The distribution PFS will be estimated using the method of Kaplan-Meier. Comparisons of event time distributions between arms will be summarized by hazard ratios and 80% confidence intervals (consistent with 1-sided 10% level testing) from a Cox Proportional hazards model including the stratification factors.

  From date of randomization to date of first documentation of progression, symptomatic deterioration, or death due to any cause, assessed up to 3 years

• Response rate of SG against historical response rates (Single arm evaluation)

  Within each treatment arm, the objective is to evaluate if response rates show activity beyond standard of care, which generally would be single agent chemotherapy or docetaxel combined with ramucirumab. With 35 eligible and evaluable participants per arm, the evaluation has 90% exact power to rule out a 10% response rate using a 1-sided 5% level test (the exact level is 5.1% based on design assumptions), if the true response rate were at least 29%. The observation of at least 7 participants with a response (a 20% response rate) would be considered evidence to rule out a 10% response rate.

  Up to 3 years

• Response rate of I against historical response rates (Single arm evaluation)

  Within each treatment arm, the objective is to evaluate if response rates show activity beyond standard of care, which generally would be single agent chemotherapy or docetaxel combined with ramucirumab. With 35 eligible and evaluable participants per arm, the evaluation has 90% exact power to rule out a 10% response rate using a 1-sided 5% level test (the exact level is 5.1% based on design assumptions), if the true response rate were at least 29%. The observation of at least 7 participants with a response (a 20% response rate) would be considered evidence to rule out a 10% response rate.

  Up to 3 years

• Response rate of SG-I against historical response rates (Single arm evaluation)

  Within each treatment arm, the objective is to evaluate if response rates show activity beyond standard of care, which generally would be single agent chemotherapy or docetaxel combined with ramucirumab. With 35 eligible and evaluable participants per arm, the evaluation has 90% exact power to rule out a 10% response rate using a 1-sided 5% level test (the exact level is 5.1% based on design assumptions), if the true response rate were at least 29%. The observation of at least 7 participants with a response (a 20% response rate) would be considered evidence to rule out a 10% response rate.

  Up to 3 years

Secondary Outcomes (10)

• Rate of dose-limiting toxicities among participants treated with SG-I in the safety run-in analysis population

  During the first cycle of treatment (21 days)

• Response rates

  Up to 3 years

• Response rates

  Up to 3 years

• Overall survival (OS)

  From date of randomization to date of death due to any cause, assessed up to 3 years

• OS

  From date of randomization to date of death due to any cause, assessed up to 3 years

Study Arms (3)

Arm 1 (ivonescimab, sacituzumab govitecan)

EXPERIMENTAL

Patients receive ivonescimab IV over 1-2 hours on day 1 of each cycle and sacituzumab govitecan IV over 1-3 hours on day 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Ivonescimab; Procedure: Magnetic Resonance Imaging; Biological: Sacituzumab Govitecan

Arm 2 (sacituzumab govitecan)

EXPERIMENTAL

Patients receive sacituzumab govitecan IV over 1-3 hours on day 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Sacituzumab Govitecan

Arm 3 (ivonescimab)

EXPERIMENTAL

Patients receive ivonescimab IV over 1-2 hours on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Ivonescimab; Procedure: Magnetic Resonance Imaging

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm 1 (ivonescimab, sacituzumab govitecan); Arm 2 (sacituzumab govitecan); Arm 3 (ivonescimab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm 1 (ivonescimab, sacituzumab govitecan); Arm 2 (sacituzumab govitecan); Arm 3 (ivonescimab)

Ivonescimab BIOLOGICAL

Given IV

Also known as: AK 112, AK-112, AK112, Anti-PD-1/Anti-VEGF Bispecific Antibody AK112, Anti-PD-1/VEGF Bispecific Antibody AK112, PD-1/VEGF Bispecific Antibody AK112, SMT 112, SMT-112, SMT112

Arm 1 (ivonescimab, sacituzumab govitecan); Arm 3 (ivonescimab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm 1 (ivonescimab, sacituzumab govitecan); Arm 2 (sacituzumab govitecan); Arm 3 (ivonescimab)

Sacituzumab Govitecan BIOLOGICAL

Given IV

Also known as: hRS7-SN38 Antibody Drug Conjugate, IMMU 132, IMMU-132, IMMU132, RS7 SN38, RS7-SN38, RS7SN38, Sacituzumab Govitecan-hziy, Trodelvy

Arm 1 (ivonescimab, sacituzumab govitecan); Arm 2 (sacituzumab govitecan)

Eligibility Criteria

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

You may qualify if:

• Participants must have been assigned to S1900N by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1900N is determined by submission of documentation of NSCLC harboring an actionable genomic alteration (AGA) in the LUNGMAP protocol. AGA is defined in this protocol as an activating driver alteration with an approved targeted therapy for lung cancer in one of the following genes: ALK, EGFR, HER2 (ERBB2), MET, NTRK, RET, and ROS1.
• Participants must have measurable disease documented by CT or MRI. The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to randomization. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to randomization. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to randomization.
• Participants must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to randomization.
• Participants with spinal cord compression or brain metastases must not have residual neurological dysfunction, unless no further recovery is expected, and the participant has been stable on weaning doses of corticosteroids (≤ 10 mg daily prednisone or equivalent) prior to randomization. Participants with spinal cord compression or brain metastases that require local treatment must have received local treatment to these metastases and remained clinically controlled and asymptomatic for at least 7 days following stereotactic radiation and/or 14 days following whole brain radiation, and prior to randomization.
• Participants must not have leptomeningeal disease that requires CNS-specific treatment prior to randomization and must not be planning to receive the CNS-specific treatment while on study.
• Participants must have progressed (in the opinion of the treating physician) during or following the most recent line of systemic therapy.
• Participants must have previously received an appropriate targeted therapy for the lung cancer AGA (ALK, EGFR, HER2 (ERBB2), MET, NTRK, RET, and ROS1).
• Participants must have previously received platinum-based chemotherapy for stage IV or recurrent disease.
• Participants must have received no more than (\<=) 3 lines of prior cytotoxic therapy (including chemotherapy, antibody-drug conjugates) for NSCLC.
• Participants must not have received prior TROP2-targeted antibody-drug conjugate or a systemic therapy containing sacituzumab govitecan/SN-38.
• Participants must not have received prior anti-PD-1 or anti-PD-L1 antibody therapy.
• Participants must not have received any systemic lung cancer therapy (except orally administered drugs) within 21 days prior to randomization. Orally administered lung cancer therapies must not have been administered within 10 days prior to randomization.
• Participants must have completed any prior radiation therapy within 7 days prior to randomization.
• Participants must have recovered (≤ Grade 1) from any side effects of prior therapy (except for alopecia) prior to randomization.
• Participants must not be planning to receive any concurrent systemic therapy (e.g. chemotherapy, immunotherapy, targeted therapy etc) for lung cancer treatment while receiving treatment on this study.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; sacituzumab govitecan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Susan C Scott

  SWOG Cancer Research Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2026
• First Posted: February 6, 2026
• Study Start (Estimated): August 7, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 1, 2029
• Last Updated: February 6, 2026

Record last verified: 2026-01