NCT04585035

Brief Summary

This is a phase 1/2, open label study of D-1553 single agent and combination treatment to assess the safety and tolerability, identify the MTD and RP2D, evaluate the PK properties and antitumor activities in subjects with advanced or metastatic solid tumor with KRasG12C mutation.

Trial Health

58
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
180

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Oct 2020

Longer than P75 for phase_1

Geographic Reach
4 countries

25 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 27, 2020

Completed
5 days until next milestone

Study Start

First participant enrolled

October 2, 2020

Completed
12 days until next milestone

First Posted

Study publicly available on registry

October 14, 2020

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2024

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2025

Completed
Last Updated

March 18, 2025

Status Verified

October 1, 2024

Enrollment Period

3.6 years

First QC Date

September 27, 2020

Last Update Submit

March 13, 2025

Conditions

Outcome Measures

Primary Outcomes (3)

  • Subject incidence of Dose-limiting toxicities (DLT)

    through out the DLT period, approximately 21 days

  • Number of subjects participants with adverse events

    Through study completion, approximately 3 years

  • Plasma concentration of D-1553 as a single agent or in combination with other therapies in subjects wiht advanced or metastatic solid tumors with KRas G12C mutation.

    Through study completion, approximately 3 years

Study Arms (3)

Dose escalation of D-1553 monotherapy

EXPERIMENTAL

Phase 1a will evaluate up to 7 sequential cohorts with different doses of D-1553 to determine safety, tolerability, MTD and RDE in patients with solid tumors with KRasG12C mutation.

Drug: D-1553

Dose combination of D-1553 with other therapies

EXPERIMENTAL

Phase 1b will determine the MTD of D-1553 in combination treatment in subjects with advanced or metastatic NSCLC, CRC and other solid tumors. There are multiple groups in Phase 1b for different tumor types and treatment combinations to evaluate safety, MTD and RP2D.

Drug: D-1553Drug: D-1553 in combination with Drug: pembrolizumab, Drug:KEYTRUDA® , Drug: cetuximab, Drug: other

Phase 2 of D-1553 monotherapy and combination therapies

EXPERIMENTAL

The Phase 2 portion is a multi-arm, parallel, open label study to evaluate the efficacy of D- 1553 single agent and combination treatments in subjects with advanced or metastatic solid tumors with KRas G12C mutation. Enrollment into phase 2 will be opened after confirmation of the recommended phase 2 dose.

Drug: D-1553Drug: D-1553 in combination with Drug: pembrolizumab, Drug:KEYTRUDA® , Drug: cetuximab, Drug: other

Interventions

D-1553DRUG

D-1553 is a novel, targeted KRasG12C inhibitor that is being developed as a potential oral agent for advanced or metastatic solid tumors with KRasG12C mutation.

Dose combination of D-1553 with other therapiesDose escalation of D-1553 monotherapyPhase 2 of D-1553 monotherapy and combination therapies

Standard treatment of solid tumor, NSCLC or CRC

Dose combination of D-1553 with other therapiesPhase 2 of D-1553 monotherapy and combination therapies

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subject with histologically proven, locally advanced, unresectable and/or metastatic solid tumor, for which no standard treatment is available, or the subject is refractory to or intolerant of existing standard treatment.
  • Subject has KRasG12C mutation in tumor tissue or other bio-specimens containing cancer cells or DNA. Historical, local laboratory result (up to 5 years prior to this study) can be used for Phase 1 subjects. Phase 2 subjects must be tested for KRasG12C mutation by a central laboratory.
  • Subject has tumor type requirement as follows: advanced or metastatic solid tumors including NSCLC and CRC.
  • Subject has measurable disease according to RECIST, v1.1.

You may not qualify if:

  • Subject with unstable or progressive central nervous system (CNS) metastases.
  • Subject with acute myocardial infarction, severe/unstable angina; or with cardiac insufficiency of New York Heart Association Functional Classification Grade 2 or above.
  • Subject has corrected QT interval using Fridericia's formula (QTcF) prolongation at rest, where the mean QTc interval is \> 480 msec based on triplicate measurements of electrocardiogram (ECG).
  • Subject with stroke or other severe cerebrovascular diseases within 12 months before enrollment;
  • Subject with interstitial lung disease or acute lung infection not yet recovered including but not limited to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection;
  • Subject has any history or evidence of substance abuse or medical, psychological or social conditions that may, in the opinion of the investigator, interfere with participation in the study or evaluation of the study results.
  • Subject has impaired gastrointestinal (GI) function or GI diseases that may significantly alter the absorption or metabolism of oral medications.
  • Subject has unresolved toxicities from prior anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI CTCAE, v5.0, Grade ≤ 1 (Grade ≤ 2 for peripheral neuropathy).
  • Subject had major surgery within 4 weeks prior to study intervention administration or last dose of palliative radiation therapy within 2 weeks prior to study intervention administration.
  • Subject is pregnant or lactating.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

Research Site

Fresno, California, 93720, United States

Location

Research Site

Orange, California, 92868, United States

Location

Research Site

San Francisco, California, 94158, United States

Location

Research Site

Louisville, Kentucky, 40202, United States

Location

Research Site

Detroit, Michigan, 48202, United States

Location

Research Site

New York, New York, 11432, United States

Location

Research Site

Portland, Oregon, 97213, United States

Location

Research Site

Blacktown, New South Wales, 2148, Australia

Location

Research Site

East Albury, New South Wales, 2640, Australia

Location

Research Site

Kogarah, New South Wales, 2217, Australia

Location

Research Site

Waratah, New South Wales, 2298, Australia

Location

Research Site

Woodville South, South Australia, 5011, Australia

Location

Research Site

Fitzroy, Victoria, 3065, Australia

Location

Research Site

Frankston, Victoria, 3199, Australia

Location

Research Site

Malvern, Victoria, 3144, Australia

Location

Research Site

Nedlands, Western Australia, 6009, Australia

Location

Research Site

Seogu, Busan, 602-715, South Korea

Location

Research Site

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

Research Site

Seoul, 06591, South Korea

Location

Research Site

Seoul, 138-736, South Korea

Location

Research Site

Seoul, 152-703, South Korea

Location

Research Site

Tainan, 704, Taiwan

Location

Research Site

Taipei, 10002, Taiwan

Location

Research Site

Taipei, 11217, Taiwan

Location

Research Site

Taoyuan, 333, Taiwan

Location

Related Publications (1)

  • Ruan DY, Wu HX, Xu Y, Munster PN, Deng Y, Richardson G, Yan D, Lee MA, Lee KW, Pan H, Hager S, Li X, Wei S, Hou X, Underhill C, Millward M, Nordman I, Zhang J, Shan J, Han G, Grewal J, Gadgeel SM, Sanborn RE, Huh SJ, Hu X, Zhang Y, Xiang Z, Luo L, Xie X, Shi Z, Wang Y, Zhang L, Wang F, Xu RH. Garsorasib, a KRAS G12C inhibitor, with or without cetuximab, an EGFR antibody, in colorectal cancer cohorts of a phase II trial in advanced solid tumors with KRAS G12C mutation. Signal Transduct Target Ther. 2025 Jun 17;10(1):189. doi: 10.1038/s41392-025-02274-z.

MeSH Terms

Interventions

pembrolizumabCetuximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Phase Ia dose escalation portion of the study followed by a Phase Ib dose combination portion. Phase 2 will consist of 5 treatment arms.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 27, 2020

First Posted

October 14, 2020

Study Start

October 2, 2020

Primary Completion

April 30, 2024

Study Completion

December 1, 2025

Last Updated

March 18, 2025

Record last verified: 2024-10

Data Sharing

IPD Sharing
Will not share

Locations