## Protocol Section
### Identification Module
**NCT ID:** NCT06435455

**Brief Title:** GH21 Combined With D-1553 With Advanced Solid Tumors

**Official Title:** A Multicenter, Open-label Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of GH21 Combined With D-1553 in Patients With Advanced or Metastatic Solid Tumors Harboring KRAS G12C Mutation

#### Organization Study ID Info
**ID:** GH21C203
#### Organization
**Class:** OTHER
**Full Name:** Suzhou Genhouse Bio Co., Ltd.
### Status Module
#### Completion Date
**Date:** 2027-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-30

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-09-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-24
**Study First Submit QC Date:** 2024-05-24
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Zhejiang Cancer Hospital

#### Lead Sponsor

**Class:** OTHER

**Name:** Suzhou Genhouse Bio Co., Ltd.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This s a multi-center, open-label phase Ib/II study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of GH21 combined with D-1553 in patients with advanced or metastatic solid tumors harboring KRAS G12C mutation.

**Detailed Description:** This study includes 2 parts: dose escalation(Phase Ib) and dose expansion (Phase II). The objective of the dose escalation part is to evaluate the safety, tolerability and pharmacokinetics of GH21 in combination with D-1553 in patients with advanced solid tumors harboring KRAS G12C mutation and to determine the RP2D for the combination therapy. In the dose expansion part, preliminary efficacy and safety of the combination therapy at the RP2D will be further explored in patients with specific cancer harboring KRAS G12C mutation.

### Conditions Module

**Conditions:**

- KRAS G12C Mutant Solid Tumors

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 126

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** GH21 capsules combined with D-1553 tablets were administrated orally

**Intervention Names:**

- Drug: GH21+D-1553

**Label:** "GH21 + D-1553" Group

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- "GH21 + D-1553" Group

**Description:** The combination of GH21 and D-1553 is expected to benefit solid tumors harboring the KRASG12C mutation.

**Name:** GH21+D-1553

**Other Names:**

- GH21 capsules combined with D-1553 tablets

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Incidence of dose limiting toxicities (DLTs) in the dose escalation phase.

**Measure:** Number of participants with dose limiting toxicities

**Time Frame:** 2 years

**Description:** All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs , etc

**Measure:** Number of participants with adverse events

**Time Frame:** 2 years

#### Secondary Outcomes

**Description:** ORR is defined as the proportion of participants with complete response or partial response (CR+PR)

**Measure:** Objective response rate (ORR)

**Time Frame:** 2 years

**Description:** DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first.

**Measure:** Duration of response (DOR)

**Time Frame:** 2 years

**Description:** DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD).

**Measure:** Disease Control Rate (DCR)

**Time Frame:** 2 years

**Description:** PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression or death which occurs first.

**Measure:** Progression-free survival (PFS)

**Time Frame:** 2 years

**Description:** OS is defined as the interval of time between the date of first treatment until death, loss to follow up or termination of the study by the sponsor

**Measure:** Overall survival (OS)

**Time Frame:** 2 years

**Description:** Peak Plasma concentration

**Measure:** Cmax

**Time Frame:** 2 years

**Description:** Time to achieve Cmax

**Measure:** Tmax

**Time Frame:** 2 years

**Description:** Area under the plasma concentration-time curve

**Measure:** AUC

**Time Frame:** 2 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* The patient or his legal representative is able to understand and voluntarily sign a written informed consent (before commencing this study and any research procedure);
* Age ≥18 years old, male or female;
* Dose escalation stage (Stage Ib) : advanced solid tumors with KRAS G12C mutation in patients who have previously failed standard therapy or have no standard therapy or are intolerant to standard therapy.
* Dose Expansion Phase (Phase II) :

Cohort 1: advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation; .

Cohort 2: G12Ci naïve advanced solid tumors with KRAS G12C mutation. Cohort 3: G12Ci treated advanced solid tumors with KRAS G12C.

* The patient must have at least one measurable lesion that meets the RECIST v1.1 definition (tumor lesion located in the area of prior radiotherapy or other local regional treatment site is generally not considered as a measurable lesion unless there is definite progression of the lesion);
* Expected survival ≥3 months;
* ECOG Physical strength score: 0-1;
* The patient must have adequate organ function, defined as follows:

blood Absolute neutrophil count (ANC) ≥1.5×109/L within 14 days without the support of granulocyte colony-stimulating factor; No blood transfusion within 14 days, platelets ≥100×109/L without the use of thrombopoietin (TPO) and interleukin-11 (IL-11); Hemoglobin ≥90 g/L without blood transfusion within 14 days, without erythropoietin (EPO); kidney Serum creatinine ≤1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 60ml/min calculated using the modified Cockcroft-Gault equation or eGFR≥ 60ml/min estimated by the MDRD equation; liver albumin ≥3.0 g/dL; Total bilirubin ≤1.5×ULN; In patients with liver metastasis, total bilirubin ≤2.5×ULN; AST/ALT≤2.5 x ULN; In patients with liver metastasis, AST/ALT≤5×ULN; Coagulation function International Normalized ratio (INR) and prothrombin time (PT) ≤1.5×ULN, unless the patient is being treated with anticoagulants (INR\<2.5×ULN) and PT or PTT is within the therapeutic range for which the anticoagulant is intended to be used; Activated partial thromboplastin time (APTT) ≤1.5×ULN, unless the patient is being treated with an anticoagulant (APTT\<2.5×ULN) and PT or PTT is within the therapeutic range for which the anticoagulant is intended to be used.

* Fertile men and women of childbearing age must agree to use reliable contraception (hormonal or barrier or abstinence) from the time they sign an informed consent until 6 months after the final administration of the investigational drug. Pregnancy test results for women of reproductive age must be negative within ≤7 days before the first study drug administration.

Exclusion Criteria:

* Received biological agents of chemotherapy and anti-tumor therapy within 3 weeks before the first administration, and received anti-tumor drugs such as radiotherapy and endocrine therapy within 4 weeks before the first administration, except for the following:

nitrosourea or mitomycin C within 6 weeks prior to first use of the study drug; Oral fluorouracil, small molecule targeted drugs, and Chinese herbal medicines or proprietary Chinese medicines with anti-tumor indications within 5 half-lives or 2 weeks prior to the first use of the study drug (whichever is shorter); local palliative radiotherapy within 2 weeks prior to the first use of the study drug;

* Received other investigational drugs or treatments that are not on the market within 5 half-lives or 4 weeks (whichever is shorter) prior to initial administration;
* Had major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to the first dose, or required elective surgery during the trial;
* Use of CYP3A4 or P-gp suppressor or strong inducer within 2 weeks or 5 half-lives prior to initial administration;
* There is evidence of the following heart diseases:

acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting, cerebrovascular accident, or transient ischemic attack within 6 months before first administration; Grade III-IV heart failure based on the New York Heart Association Cardiac Function Scale at screening; During screening, echocardiography (ECHO) showed left ventricular ejection fraction (LVEF) ≤50%.

Fridericia adjusted QT interval (QTcF) ≥450ms (male), ≥470ms (female) at screening; The presence of poorly controlled hypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg) after medication at screening;

* Has difficulty swallowing or has a gastrointestinal disease or other malabsorption condition that affects drug absorption, such as intestinal obstruction, Crohn's disease, ulcerative colitis, short bowel syndrome, gastric emptying disorder, or has severe gastrointestinal related toxicity before first administration and does not recover below grade 2; Or confirmed clinically significant or acute gastrointestinal disease;
* Uncontrolled pleural effusion, pericardial effusion, or pleural effusion requiring repeated drainage (once a month or more frequently);
* Patients with active brain metastases or with symptoms of active central nervous system metastases, including headache, vomiting, and vertigo, are eligible only if they meet all of the following criteria and are asymptomatic and have treated or untreated CNS lesions:

The presence of measurable lesions outside the CNS as determined by RECIST v1.1; Stable brain metastases after treatment, defined as no evidence of disease progression or bleeding during the 28 days prior to initiation of treatment and discontinuation of steroid hormones and other therapeutic agents for at least 14 days prior to enrollment;

* Patients with interstitial pneumonia, or any evidence of clinically active interstitial lung disease, within 6 months prior to first dosing;
* Arteriovenous thrombosis events, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism, occurred within 6 months prior to initial administration;
* Have a history of other malignancies (except skin squamous cell carcinoma in situ that has been cured and has not recurred for 5 years, basal cell carcinoma and cervical carcinoma in situ, etc., which are considered by researchers to be eligible for inclusion; Dose escalation phase, except for those deemed acceptable by the investigator);
* Patients who have a history of severe allergy, or have a history of allergy to the experimental drug/any excipient/combination drug, or have a history of allergy to multiple drugs;
* Hepatitis B virus infection (HBsAg positive and DNA copy number \>1000 IU/ml); Or infected with hepatitis C virus (HCV antibody positive and HCV RNA \> the upper limit of normal); Or infected with human immunodeficiency virus (HIV antibody positive); Or infected with treponema pallidum (defined as TP-Ab positive);
* There is an active infection (≥ grade 2) requiring anti-infective treatment or an unexplained fever exceeding 38 ° C within 28 days before the first dose;
* Active stage of autoimmune disease as determined by the investigator within 28 days before the first dose;
* Any toxicity from previous antitumor therapy prior to initial administration has not returned to CTCAE 5.0 rating ≤ Class 1 (unless hair loss, grade 2 peripheral neuropathy, and/or other grade ≤2 adverse events that do not pose a safety risk);
* Pregnant and lactating women;
* The investigator considers that there are any clinical or laboratory abnormalities or other reasons to be unsuitable for participating in this clinical study.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** tangjieqi@genhousebio.com

**Name:** Jieqi Tang, bachelor

**Phone:** +8613311557758

**Role:** CONTACT

**Contact 2:**

**Email:** zjccgcp_phase1@126.com

**Name:** Zhengbo Song, Doctorate

**Phone:** +8613857153345

**Role:** CONTACT

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

### Misc Info Module

- Version Holder: 2024-05-31
