Study to Evaluate D-1553 in Subjects With Solid Tumors

NCT ID: NCT04585035

Last Updated: 2025-03-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-02
• Study Completion Date: 2025-12-31

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.

Conditions

Solid Tumor, Adult; NSCLC; CRC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation of D-1553 monotherapy

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.

Group Type: EXPERIMENTAL

D-1553

Intervention Type: DRUG

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 therapies

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.

Group Type: EXPERIMENTAL

D-1553

Intervention Type: DRUG

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.

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

Intervention Type: DRUG

Standard treatment of solid tumor, NSCLC or CRC

Phase 2 of D-1553 monotherapy and combination therapies

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.

Group Type: EXPERIMENTAL

D-1553

Intervention Type: DRUG

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.

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

Intervention Type: DRUG

Standard treatment of solid tumor, NSCLC or CRC

Interventions

D-1553

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.

Intervention Type: DRUG

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

Standard treatment of solid tumor, NSCLC or CRC

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

InventisBio Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Fresno, California, United States

Research Site

Orange, California, United States

Research Site

San Francisco, California, United States

Research Site

Louisville, Kentucky, United States

Research Site

Detroit, Michigan, United States

Research Site

New York, New York, United States

Research Site

Portland, Oregon, United States

Research Site

Blacktown, New South Wales, Australia

Research Site

East Albury, New South Wales, Australia

Research Site

Kogarah, New South Wales, Australia

Research Site

Waratah, New South Wales, Australia

Research Site

Woodville South, South Australia, Australia

Research Site

Fitzroy, Victoria, Australia

Research Site

Frankston, Victoria, Australia

Research Site

Malvern, Victoria, Australia

Research Site

Nedlands, Western Australia, Australia

Research Site

Seogu, Busan, South Korea

Research Site

Seongnam-si, Gyeonggi-do, South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Tainan City, , Taiwan

Research Site

Taipei, , Taiwan

Research Site

Taipei, , Taiwan

Research Site

Taoyuan, , Taiwan

Countries

United States; Australia; South Korea; Taiwan

References

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.

Reference Type: DERIVED

PMID: 40523897 (View on PubMed)

Other Identifiers

KEYNOTE-C15 MK3475-C15

Identifier Type: OTHER

Identifier Source: secondary_id

D1553-101

Identifier Type: -

Identifier Source: org_study_id