Adjuvant ctDNA-Adapted Personalized Treatment in Early Stage NSCLC (ADAPT-E)

NCT04585477 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 3 other identifiers: IRB-54622LUN0115NCI-2021-03445
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

In this study circulating tumor DNA (ctDNA) blood testing is used to detect the residual blood cancer. If residual cancer using this blood test is detected there may be at higher risk of having the cancer return. The study is going to test whether or not the number of circulating cancer cells detected in the blood can be reduced by administration durvalumab after the standard treatment if you are tested positive for the residual cancer.

Conditions

Non-small Cell Lung Cancer; Non-small Cell Lung Cancer Stage II; Non-small Cell Lung Cancer Stage III; Non-small Cell Lung Cancer Stage I

Outcome Measures

Primary Outcomes (1)

• Decrease in ctDNA Level

  Change in minimal residual disease (MRD) will be assessed on the basis of reduction of circulating tumor DNA (ctDNA) in the blood of participants in Cohort 1 MRD+ only. ctDNA is an indicator of MRD. The outcome will be reported as the number of participants who have a ≥ 3-fold drop in ctDNA levels after 2 cycles of durvalumab treatment, a number without dispersion.

  8 weeks

Secondary Outcomes (4)

• Presence or absence of detectable ctDNA

  8 weeks

• Overall survival (OS)

  12 months

• Disease-free survival (DFS)

  8 weeks

• Related Adverse Events

  12 months

Study Arms (2)

Cohort 1 minimal residue disease positive(MRD+)

EXPERIMENTAL

Subjects with detectable ctDNA (MRD+) will receive up to 12 cycles of durvalumab (1500mg dose by intravenous (by vein) injection every 28 days). ctDNA will be re checked following 2 cycles (8 weeks) of durvalumab and compared to baseline levels. In the absence of progression or toxicity after 2 cycles, subject will continue with durvalumab to complete 1 year of treatment about 10 additional cycles). Subjects will be monitored for secondary endpoints of progression free survival (PFS) and overall survival (OS).

Device: AVENIO ctDNA Surveillance Kit; Drug: Durvalumab; Drug: Durvalumab (Imfinzi) alone or in combination with platinum-based chemotherapy

Cohort 2 minimal residue disease negative (MRD-)

ACTIVE COMPARATOR

Subjects with undetectable ctDNA (MRD) will receive Standard of care and no treatment

Device: AVENIO ctDNA Surveillance Kit; Drug: Durvalumab (Imfinzi) alone or in combination with platinum-based chemotherapy

Interventions

Durvalumab DRUG

Participants in the intervention arm will receive Durvalumab (1500 mg IV every 4 weeks for up to 12 months) as monotherapy or 20mg/kg if weight is 30kg or less.

Also known as: IMFINZI, MEDI4736

Cohort 1 minimal residue disease positive(MRD+)

Durvalumab (Imfinzi) alone or in combination with platinum-based chemotherapy DRUG

Participants in the intervention arm (Cohort 1 MRD+) will receive a fixed dose of Durvalumab (1500 mg IV every 4 weeks for up to 12 months), either as monotherapy or in combination with a platinum-based chemotherapy regimen (investigator's choice). Platinum-based chemotherapy options include carboplatin, cisplatin, pemetrexed, paclitaxel, or nab-paclitaxel, administered per standard of care for up to 4 cycles.

Cohort 1 minimal residue disease positive(MRD+); Cohort 2 minimal residue disease negative (MRD-)

AVENIO ctDNA Surveillance Kit DEVICE

Roche Sequencing and Life Science kit to detect minimal residue disease (MRD)

Also known as: The AVENIO ctDNA Surveillance Kit

Cohort 1 minimal residue disease positive(MRD+); Cohort 2 minimal residue disease negative (MRD-)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically (histologically or cytologically proven) NSCLC. Tumors with any component of small cell lung cancer are not allowed.
• Adenocarcinoma patients must NOT be positive for EGFR Exon 19 deletion or L858R mutation, or ALK or ROS1 rearrangement.
• AJCC 8th edition clinical or pathological stage IA2 to IIIC or locoregionally recurrent disease. Stage IA1 tumors are excluded unless recurrent with radiographic solid component -or- pathologic invasive component of \> 10 mm.
• Received curative intent therapy with surgery and/or radiation. Note: May have received chemotherapy.
• Completed all intended therapy (surgery, radiation, and/or chemotherapy) - AND- no more than 32 weeks has elapsed after the last day of this therapy.
• No known current radiographic or pathologic residual/recurrent disease (in the investigator's opinion) after completion of all intended therapy (for example, positive margins after surgery without adjuvant radiotherapy, or unequivocal radiographic evidence of residual or recurrent disease)
• Pre-treatment tumor tissue or tumor DNA sample is believed to be available for analysis
• Not received immunotherapy (PD-1, PD-L1, or CTLA-4 antibodies) or be intended to receive immunotherapy, apart from this study.
• Not received another systemic anti-cancer investigational product during the 4 weeks prior to enrollment.
• Aged 18 years or older
• ECOG Performance Status of 0 or 1 (Appendix B)
• Life expectancy ≥ 12 weeks
• Acceptable laboratory parameters:
• Absolute neutrophil count \> 1.0 x 109/L
• Platelets \> 75 x 109/L

You may not qualify if:

• Involvement in the planning and/or conduct of the study
• History of Grade 3 or higher pneumonitis from prior radiation; patients with grade 2 radiation pneumonitis may be considered for enrollment with permission from the Protocol Director or Co-Director.
• History of another primary malignancy and currently undergoing active treatment Exception: May participate if receiving adjuvant endocrine therapy for breast or prostate cancer.
• Expected to require ongoing chronic treatment with systemic immunosuppressive medication after enrollment.
• Exceptions: intranasal, inhaled, or topical corticosteroids or systemic corticosteroids at physiological doses, not to exceed 10 mg/day of prednisone equivalent
• Subjects with Grade \> 2 neuropathy will be evaluated on a case by case basis after consultation with the Protocol Director / Principal Investigator
• Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by treatment with durvalumab may be included (ie, hearing loss) with permission from the Protocol Director / Co-Director.
• Active or prior documented autoimmune or inflammatory disorders which could limit the subjects ability to receive durvalumab on the study (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis; Graves' disease; rheumatoid arthritis; hypophysitis; uveitis; etc\]). The following may be taken in to considerations as exceptions to this criterion:
• Vitiligo or alopecia
• Hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Chronic skin condition not requiring systemic therapy
• Those without active disease in the last 5 years may be included with permission from the Protocol Director / Co-Director.
• Celiac disease controlled by diet alone
• History of primary immunodeficiency
• History of organ transplant requiring therapeutic immunosuppression

Sponsors & Collaborators

• Stanford University: lead
• AstraZeneca: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Single Person; Platinum Compounds

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Inorganic Chemicals

Study Officials

• Joel W Neal, MD,PhD

  Stanford Universiy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Lundi, BS

CONTACT

650 723-1002; llundi@stanford.edu

Study Design

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

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 14, 2020
• Study Start: April 8, 2021
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)