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NeoplasmsPhase 1NCT04006301

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation

A Phase 1 study testing JNJ-74699157 in people with Neoplasms and Advanced Solid Tumors, run by Janssen Research & Development, LLC at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
JNJ-74699157
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
7 sitesin 2 countries
Study dates
26 Jul 2019to 13 Jul 2020
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

  • Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation in tumor tissue or blood
  • Histological documentation of disease: Part 1: Histologically or cytologically confirmed solid tumor malignancy that is metastatic or unresectable, Part 2: (a) unresectable, locally advanced (Stage IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC), (b) Solid tumor malignancy other than NSCLC that is metastatic or unresectable
  • Received or was ineligible for standard treatment options. For NSCLC: previously received a platinum-containing chemotherapy regimen and an anti- programmed death-ligand 1 (PD1/PDL1) antibody, unless participant refused or was ineligible to receive such therapy; and for colorectal cancer (CRC): previously received at least 2 prior lines of therapy, including a fluoropyrimidine, oxaliplatin, and irinotecan, unless participant refused or was ineligible to receive such therapy. For Participants in France only: NSCLC: Previously received a platinum-containing chemotherapy regimen and an anti-PD1/PDL1 antibody or was ineligible to receive such therapy. CRC: Previously received at least 2 prior lines of therapy, including a fluoropyrimidine, oxaliplatin, and irinotecan or was ineligible to receive such therapy
  • Measurable or evaluable disease: Part 1: either measurable or evaluable disease, Part 2: At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

Who cannot join

  • Symptomatic brain metastases or known leptomeningeal disease; asymptomatic brain metastases are allowed if they have been treated, have been stable for greater than or equal to (>=) 4 weeks as documented by radiographic imaging, and do not require prolonged (greater than [>]14 days) systemic corticosteroid therapy. Participants who have had complete surgical resection of or received stereotactic radiosurgery to less than or equal to (<=) 3 metastatic lesions will be permitted to enroll in the study within 14 days of such treatment if they have recovered from treatment, are clinically stable, and do not require prolonged systemic corticosteroid therapy as noted above
  • Prior treatment with an inhibitor specific to KRAS G12C
  • Prior solid organ transplantation
  • History of malignancy (other than the disease under study) within 2 years before the first administration of study drug. Exceptions include squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 2 years
  • Inability to take an orally administered drug, or medical disorder or prior surgical resection that may affect the absorption of the study drug. Such conditions include, but are not limited to, malabsorption syndrome, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or resection of the stomach or small bowel. If any of these conditions exist, the investigator should discuss with the sponsor to determine participant eligibility

Trial locations and contacts

7 sites in 2 countries.

7 sites in 2 countries

United States4 sites

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • NEXT Oncology

    San Antonio, Texas, 78229

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • H. Lee Moffitt Cancer & Research Institute

    Tampa, Florida, 33612

Other trials in United States

France3 sites

  • Centre Leon Bérard

    Lyon, 69373

  • Hopital de la Timone

    Marseille, 13885

  • Institut Gustave Roussy

    Villejuif, 94800

Other trials in France

About this study

Official title: A First-in-Human Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of JNJ-74699157 in Participants With Advanced Solid Tumors Harboring the KRAS G12C Mutation

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion).

Read the detailed description

KRAS is one of the most frequently mutated genes in human cancer. KRAS mutations lead to activation of cellular signaling that promotes tumor growth, and KRAS may therefore be a candidate target for anticancer therapy. This study will evaluate JNJ-74699157, a potent and specific, orally bioavailable inhibitor of the glycine-to-cysteine (G12C) mutant KRAS protein, which is found in non-small cell lung cancers and other solid tumor types. This study will enroll participants with advanced solid tumors harboring the KRAS G12C mutation and will be conducted in 2 parts. Part 1 (Dose Escalation) will be carried out in sequential cohorts of single or multiple participants at doses assigned by the study evaluation team to determine the MTD and RP2D of JNJ-74699157. Participants in Part 2 (Dose Expansion) will receive JNJ-74699157 at the RP2D determined in Part 1 to determine the safety and preliminary antitumor activity of the RP2D. Key efficacy assessments include radiographic imaging evaluations, physical examination, and tumor markers. Safety evaluations will include monitoring of adverse events, vital signs, laboratory evaluations, cardiac monitoring and physical examination findings. The study consists of a screening phase, treatment phase, and a post-treatment follow-up phase. An end-of-treatment visit will occur within 30 days of the last dose of study drug or prior to the start of a subsequent anticancer therapy, whichever comes first. The study duration will be up to 4 years.

Being tested
JNJ-74699157
Keywords
KRAS G12C
Medical subject headings
Neoplasms, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms

What participants receive

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

  • JNJ-74699157Drug

    Also called ARS-3248

    Participants will receive JNJ-74699157 orally.

Study groups in NCT04006301
Study groupRoleWhat they receive
Part 1: Dose EscalationExperimentalParticipants with advanced solid tumors harboring the kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation will receive oral administration of JNJ-74699157. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.
Receives: Drug: JNJ-74699157
Part 2: Dose ExpansionExperimentalTwo groups of participants with either non-small cell lung cancer or other solid tumors harboring KRAS G12C mutation will receive JNJ-74699157 at RP2D determined in Part 1.
Receives: Drug: JNJ-74699157

What is being measured

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

  1. Part 1: Number of Participants with Dose-Limiting Toxicity (DLT)

    DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

    Measured: Up to 2 years

  2. Part 1 and Part 2: Number of Participants with Adverse Events (AEs)

    An AE is any untoward medical occurrence in a participant who received study drug without regard to causal relationship.

    Measured: Up to 4 years

  3. Part 1 and Part 2: Number of Participants with AE's by Severity

    Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life threatening consequences; Grade 5: Death.

    Measured: Up to 4 years

  4. Part 2: Overall Response Rate (ORR)

    ORR is defined as the percentage of participants who have a partial response (PR) or better response as per RECIST v.1.1. PR criteria in solid tumors (RECIST) is greater than or equal to (>=) 30 percent (%) decrease in the sum of the diameters of all index lesions compared with baseline in 2 observations at least 4 weeks apart, in absence of new lesions or unequivocal progression of non-index lesions.

    Measured: Up to 4 years

Secondary outcomes (7)

  1. Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-74699157

    Cmax is the maximum observed plasma concentration.

    Measured: Up to 4 years

  2. Part 1 and Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-74699157

    Tmax is defined as actual sampling time to reach maximum observed plasma concentration.

    Measured: Up to 4 years

  3. Part 1 and 2: Area Under Plasma-concentration Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-last])

    AUC (0-last) is the area under the plasma concentration-time curve from time zero to last observed quantifiable concentration.

    Measured: Up to 4 years

  4. Part 1 and 2: Percentage of KRAS G12C Protein in Tumor Tissue Covalently Bound with JNJ-74699157 or its Metabolites

    Percentage of kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) protein in tumor tissue covalently bound with JNJ-74699157 or its metabolites will be evaluated using mass spectroscopy.

    Measured: Up to 4 Years

  5. Part 1: Overall Response Rate

    ORR is defined as the percentage of participants who have a PR or better response as per RECIST v.1.1. PR criteria in solid tumors (RECIST) is >=30 percent % decrease in the sum of the diameters of all index lesions compared with baseline in 2 observations at least 4 weeks apart, in absence of new lesions or unequivocal progression of non-index lesions.

    Measured: Up to 4 years

  6. Part 1 and Part 2: Duration of Response (DOR)

    DOR is defined as the duration from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease (PD), as defined in the RECIST v1.1, or death due to any cause, whichever occurs first. PD is assessed if the sum of the diameters has increased by >=20% and >=5 millimeter (mm) from nadir (including baseline if it is the smallest sum).

    Measured: Up to 4 years

  7. Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method

    Change from baseline in QTcF intervals will be assessed.

    Measured: Baseline up to 4 years

Timeline

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

  1. First posted5 Jul 2019
  2. Study start26 Jul 2019
  3. Primary completion13 Jul 2020
  4. Study completion13 Jul 2020

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04006301
Sponsor's protocol ID
CR108652
Other IDs
2019-000565-21, 74699157STM1001, 2019
Status last verified
Nov 2020
First submitted
2 Jul 2019
Last updated
6 Nov 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Publications

  • Wang J, Martin-Romano P, Cassier P, Johnson M, Haura E, Lenox L, Guo Y, Bandyopadhyay N, Russell M, Shearin E, Lauring J, Dahan L. Phase I Study of JNJ-74699157 in Patients with Advanced Solid Tumors Harboring the KRAS G12C Mutation. Oncologist. 2022 Jul 5;27(7):536-e553. doi: 10.1093/oncolo/oyab080.

    PubMed 35325211

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing JNJ-74699157 in people with Neoplasms and Advanced Solid Tumors, run by Janssen Research & Development, LLC at 7 sites in 2 countries.

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 5 inclusion and 5 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: finished, as of the sponsor's last update on 6 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, France. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Part 1: Number of Participants with Dose-Limiting Toxicity (DLT) (time frame: Up to 2 years). The study lists 4 primary outcomes in all. 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 NCT04006301, 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 6 Nov 2020.

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