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Lung CancerPhase 1NCT05848843

A Phase I Study of Adagrasib and Durvalumab for Treatment of Advanced Non-small Cell Lung Cancers and Gastro-intestinal Cancers Harboring KRAS G12C Mutations

A Phase 1 study testing Durvalumab and Adagrasib in people with Lung Cancer and Gastro-intestinal Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

To find a recommended dose of the combination of adagrasib and durvalumab that can be given to patients with cancers that have a KRAS G12C mutation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer, Gastro-intestinal Cancer
What is being tested?
Durvalumab and Adagrasib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
25 Apr 2023to 16 Jan 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For the dose confirmation cohort, histologically confirmed diagnosis of NSCLC or carcinomas of gastro-intestinal tract, including, but not limited to, colorectal adenocarcinoma, pancreatic adenocarcinoma, and cholangiocarcinoma. For the Dose Expansion cohorts, only NSCLC and colorectal adenocarcinoma histologies are eligible.
  • Presence of KRAS G12C mutation detected by assay performed in a CLIA-certified environment.
  • Metastatic disease or locally advanced disease not amenable to local therapy.
  • ECOG performance status 0 or 1.
  • Presence of measurable disease per RECIST v1.1.
  • Any number of prior lines of therapy, including prior KRAS G12C inhibitor. For the Dose Expansion cohorts, only treatment naïve NSCLC patients and colorectal adenocarcinoma patients with disease progression on prior KRAS G12Ci are eligible. NSCLC patients that completed curative intent treatment of their disease ≥6 months prior to enrollment are eligible for frontline expansion cohort as long as they have not been previously treated with a KRAS G12C inhibitor.
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  • Age ≥ 18 years.
  • Life expectancy of at least 3 months.
  • Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or, investigational agent) and radiation therapy discontinued at least 2 weeks before first dose date.
  • Recovery from the adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia and parameters superseded by other eligibility criteria [eg, laboratory parameters]).
  • Laboratory values within the screening period:
  • Absolute neutrophil count ≥ 1,000/mm3 (≥ 1.0 x 109/L)
  • Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) (if associated with liver metastases or Gilbert's disease, ≤ 3 x ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN (if associated with liver metastases, ≤ 5 x ULN)
  • Creatinine clearance ≥50 mL/min calculated using a validated prediction equation (e.g., Cockcroft-Gault, MDRD, or 24-hour urine CrCl).
  • Women of child-bearing potential (WOCBP) or men whose partner is a WOCBP agrees to use contraception while participating in this study, and for a period of 6 months following termination of study treatment (see Reproductive Health below).
  • Completed informed consent process, including signing IRB/EC-approved informed consent form.
  • Willing to comply with clinical trial instructions and requirements. Reproductive Health
  • Patients who are biologically capable of having children and sexually active must agree to use an acceptable method of contraception for the duration of the treatment period and for at least 6 months after the last dose of study treatment. The Investigator will counsel the patient on selection of contraception method and instruct the patient in its consistent and correct use. Examples of acceptable forms of contraception include:
  • Oral, inserted, injected or implanted hormonal methods of contraception, provided it has been used for an adequate period of time to ensure effectiveness.
  • Correctly placed copper containing intrauterine device (IUD).
  • Male condom or female condom used WITH a spermicide.
  • Male sterilization with confirmed absence of sperm in the post-vasectomy ejaculate.
  • Bilateral tubal ligation or bilateral salpingectomy. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.
  • The Investigator will instruct the patient to call immediately if the selected birth control method is discontinued or if pregnancy is known or suspected.
  • Note: Women are considered post-menopausal and/or not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical

Who cannot join

  • Radiation to the lung >30 Gy within 3 months prior to the first dose of study treatment.
  • Active brain metastases. Patients are eligible if brain metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to the first dose of study treatment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
  • Carcinomatous meningitis.
  • History of significant hemoptysis or hemorrhage within 4 weeks of the first dose date.
  • Active or prior documented autoimmune or inflammatory disease, as follows:
  • Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
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  • History of interstitial lung disease (ILD) or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD or pneumonitis.
  • Other medically important autoimmune disease within 2 years prior to the first dose of study treatment. NOTE: Patients with Type 1 diabetes, vitiligo, Graves' disease requiring only hormone replacement, hypothyroidism, or psoriasis not requiring systemic treatment within the past 2 years are not excluded.
  • Immunocompromising conditions, as follows:
  • Use of immunosuppressive medication within 28 days prior to the first dose of study treatment, with the exceptions of corticosteroids.
  • History of primary immunodeficiency.
  • History of allogeneic transplant.
  • Receipt of a live vaccine within 30 days prior to first dose of study treatment.
  • Known severe hypersensitivity to study drugs and/or any of its excipients.
  • Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B or C infection. Patients treated for hepatitis C with no detectable viral load are permitted.
  • Major surgery within 4 weeks prior to first dose of study treatment.
  • History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications.
  • Any of the following cardiac abnormalities:
  • Unstable angina pectoris or myocardial infarction within the past 6 months.
  • Symptomatic or uncontrolled atrial fibrillation within the past 6 months.
  • Congestive heart failure ≥NYHA Class 3 within the past 6 months.
  • Prolonged QTc interval >480 milliseconds, or immediate family or medical history of congenital Long QT Syndrome.
  • History of stroke or transient ischemic attack within 6 months prior to first dose of study treatment.
  • Ongoing need for a medication with any of the following characteristics that cannot be switched to alternative treatment prior to study entry: known risk of QT prolongation or Torsades de Pointes; substrate of CYP3A with narrow therapeutic index; strong inducer of CYP3A and/or P-gp; strong inhibitor of BCRP; and proton pump inhibitors (see Appendix 2).
  • Known or suspected presence of another malignancy that could be mistaken for the malignancy under study during disease assessments.
  • Pregnancy. WOCBP must have a negative serum or urine pregnancy test documented within the screening period prior start of study drug.
  • Breast-feeding or planning to breast feed during the study or within 6 months after the last dose of study treatment.
  • Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with the patient's participation in the study, or with the interpretation of the results.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

To find a recommended dose of the combination of adagrasib and durvalumab that can be given to patients with cancers that have a KRAS G12C mutation.

Read the detailed description

Primary Objectives:

  • To determine the safety and tolerability, and to establish the recommended dose of the adagrasib and durvalumab combination in advanced NSCLC or GI cancer patients.

Secondary Objectives:

  • To determine the objective response rate of the adagrasib and durvalumab combination for frontline treatment of advanced NSCLC harboring a KRAS G12C mutation.
  • To determine the objective response rate of the adagrasib and durvalumab combination for treatment of advanced CRC that have progressed on prior therapy with KRAS G12C inhibitors.
  • To determine duration of response (DOR) and progression-free survival (PFS) for the combination of the adagrasib and durvalumab in patients with advanced NSCLC harboring a KRAS G12C mutation.
  • To determine DOR and PFS for the combination of the adagrasib and durvalumab in patients with advanced CRC that have progressed on prior therapy with KRAS G12C inhibitors.

Exploratory Objectives:

  • To assess predictive biomarkers of response and resistance to the combination of adagrasib and durvalumab.
  • To assess mechanisms of tumor cell adaptation upon treatment with the combination of adagrasib and durvalumab.
  • To determine mechanisms of acquired resistance to the combination of adagrasib and durvalumab.
  • To assess the effect of the combination of adagrasib and durvalumab on the immune tumor microenvironment.
  • To generate cell lines and patient derived xenograft (PDX) models from tumor samples.
  • To assess the anti-tumor reactivity of tumor infiltrating lymphocytes (TIL) from tumor biopsies.
Being tested
Durvalumab, Adagrasib
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabDrug

    Given by vein (IV)

  • AdagrasibDrug

    Given by PO

Study groups in NCT05848843
Study groupRoleWhat they receive
Dose Confirmation CohortExperimentalNot described
Receives: Drug: Durvalumab; Drug: Adagrasib
Dose Expansion CohortExperimentalNot described
Receives: Drug: Durvalumab; Drug: Adagrasib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

    Measured: through study completion; an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2023
  2. Study start25 Apr 2023
  3. Primary completion16 Jan 2024
  4. Study completion16 Jan 2024

Why it stopped: 0 participant accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05848843
Sponsor's protocol ID
2022-0782
Other IDs
NCI-2023-03640
Status last verified
Jan 2024
First submitted
28 Apr 2023
Last updated
23 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Luo J, Florez N, Donnelly A, Lou Y, Lu K, Ma PC, Spira AI, Ryan D, Husain H. Adagrasib Treatment After Sotorasib-Related Hepatotoxicity in Patients With KRASG12C-Mutated Non-Small Cell Lung Cancer: A Case Series and Literature Review. JCO Precis Oncol. 2024 Apr;8:e2300644. doi: 10.1200/PO.23.00644.

    PubMed 38579193

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Durvalumab and Adagrasib in people with Lung Cancer and Gastro-intestinal Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05848843, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.

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