D-1553 for Solid Tumors

Not currently recruiting at 31 trial locations

Overseen By Jeremy Zeng

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: InventisBio Inc.

Disqualifiers: CNS metastases, Cardiac insufficiency, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called D-1553, a potential drug for individuals with advanced or spreading solid tumors, specifically those with a KRasG12C mutation. The trial aims to determine the safety and effectiveness of D-1553, both alone and in combination with other treatments. Suitable participants have tumors that standard methods cannot treat and possess the KRasG12C mutation, including cancers such as non-small cell lung cancer and colorectal cancer. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that D-1553 is generally safe for patients with solid tumors that have the KRAS G12C mutation. Patients taking D-1553 alone have mostly tolerated the treatment well, even after receiving many other treatments. Additionally, combining D-1553 with another drug, ifebemtinib, has proven manageable in terms of side effects, keeping them under control. While more research is needed, these initial findings suggest that D-1553 is relatively safe for use in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about D-1553 because it specifically targets the KRasG12C mutation, a genetic change found in several solid tumors, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Unlike other treatments that may not be mutation-specific, D-1553 aims to directly inhibit the mutant protein, potentially offering a more precise and effective approach. Additionally, the combination of D-1553 with other therapies could enhance treatment outcomes by attacking the cancer through multiple pathways. This targeted strategy could lead to better responses and fewer side effects compared to broader treatments like chemotherapy.

What evidence suggests that this trial's treatments could be effective for solid tumors with KRasG12C mutation?

Research has shown that D-1553 holds promise for individuals with solid tumors carrying the KRasG12C mutation. Earlier studies found D-1553 to be safe for patients and effective in shrinking tumors. Even for those who had undergone multiple treatments, D-1553 demonstrated efficacy, suggesting it might help when other treatments have not. In this trial, participants will receive D-1553 either as a monotherapy or in combination with other therapies. When combined with therapies like ifebemtinib, D-1553 also produced positive results, indicating its potential effectiveness as part of a combined approach against cancer. This makes D-1553 a hopeful option for those with hard-to-treat tumors. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including lung and colorectal cancer, that have no standard treatment options or haven't responded to existing treatments. Participants must have a specific mutation (KRasG12C) in their tumor and measurable disease according to certain criteria. They can't join if they have unstable brain metastases, recent heart issues or stroke, unresolved toxicities from past cancer therapy, impaired GI function affecting drug absorption, major surgery within the last month, or are pregnant.

Inclusion Criteria

My cancer is advanced or has spread to other parts of my body.

My cancer has the KRasG12C mutation.

My advanced cancer has no standard treatment options left, or I can't tolerate them.

Exclusion Criteria

I have not had a stroke or severe brain blood flow problems in the last year.

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 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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

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.

Varies

Dose Combination

Phase 1b will determine the MTD of D-1553 in combination treatment in subjects with advanced or metastatic NSCLC, CRC and other solid tumors.

Varies

Phase 2

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.

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• D-1553

Trial Overview The study is testing D-1553 alone and combined with other treatments in patients with solid tumors carrying the KRasG12C mutation. It aims to determine safe dosage levels (MTD), recommended phase 2 dosages (RP2D), how the body processes the drug (PK properties), and its effectiveness against tumors.

How Is the Trial Designed?

Group I: Phase 2 of D-1553 monotherapy and combination therapies Experimental Treatment 2 Interventions

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 II: Dose escalation of D-1553 monotherapy Experimental Treatment 1 Intervention

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 III: Dose combination of D-1553 with other therapies Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

InventisBio Inc.

Lead Sponsor

Trials

8

Recruited

900+

InventisBio Co., Ltd

Lead Sponsor

Trials

20

Recruited

1,800+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3563

Safety and efficacy of D-1553 in KRAS G12C-mutated ... Conclusions: D-1553 demonstrated a tolerable safety profile and promising monotherapy activity in pts with heavily pretreated locally advanced ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04585035

Study to Evaluate D-1553 in Subjects With Solid Tumors 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.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02208-7/fulltext

622P Safety and efficacy of ifebemtinib (IN10018) ... The combination of ifebemtinib and D-1553, as a dual-oral regimen, showed promising antitumor activity and manageable safety profile in KRAS G12C mutant solid ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT406324

Safety and efficacy of D-1553 in KRAS G12C-mutated ... Background: KRAS G12C mutation is an oncogenic driver that occurs in 3-4% of colorectal cancer (CRC). D-1553 is a novel oral and potent KRASG12C inhibitor.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10323112/

D‐1553: A novel KRASG12C inhibitor with potent and ... Here, we report the preclinical data demonstrating antitumor activity of D‐1553. Potency and specificity of D‐1553 in inhibiting GDP‐bound KRAS ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8605

Safety and efficacy of ifebemtinib (IN10018) combined with ... This study is to evaluate the safety and antitumor activity of ifebemtinib combined with D-1553 in solid tumors with KRAS G12C mutation.