Study to Evaluate the Safety and Anti-tumor Activity of SCC244

• ClinicalTrials.gov Identifier: NCT03466268
• Recruitment Status: Unknown
• First Posted: March 15, 2018
• Last Update Posted: March 11, 2020
• Sponsor: Haihe Biopharma Co., Ltd.
• Information provided by (Responsible Party): Haihe Biopharma Co., Ltd.

Study Description

Brief Summary:

This study evaluates the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of SCC244 in patients with advanced solid tumors with c-Met Alterations.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor	Drug: Glumetinib for tablet	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 113 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Trial to Assess the Safety, Pharmacokinetics, and Anti-tumor Activity of SCC244 in Subjects With Advanced Solid Tumors
• Actual Study Start Date: September 14, 2017
• Estimated Primary Completion Date: October 2021
• Estimated Study Completion Date: October 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose escalation study of Glumetinib; To determine the maximum tolerated dose (MTD) of Glumetinib	Drug: Glumetinib for tablet; Either at 100mgSD、100mgQD、200mgSD、200mgQD、400mgSD、400mgQD、300mgBID、400mgBID

Outcome Measures

Primary Outcome Measures :

1. DLT(Dose limit toxity) [ Time Frame: 35 days ]
   To evaluate the DLT in patients with advanced solid tumor
2. MTD(Max tolerance does) [ Time Frame: 35 days ]
   To evaluate the MTD in patients with advanced solid tumor
3. BED(Biological effective dose) [ Time Frame: 35 days ]
   To evaluate the BED in patients with advanced solid tumor
4. ORR(Objective response rate) [ Time Frame: 8 weeks ]
   To evaluate the ORR in patients with advanced solid tumor in Ib

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female subject ≥ 18 years of age.
2. Life expectancy ≥ 12 weeks by the Investigator.
3. In Phase Ia, histologically confirmed NSCLC (including sarcomatoid carcinoma) with c-Met alterations defined as c-Met gene amplification ≥ 5 copies or c-Met protein overexpression (IHC 3+) or c-Met exon 14 skipping mutation. No EGFR T790M mutation for subjects with c-Met gene amplification or c-Met protein overexpression; KRAS/ALK/ROS1 WT or unknown mutation/rearrangement status for subjects with c-Met exon 14 skipping mutation.
4. In Phase Ib, histologically confirmed NSCLC as in Phase Ia, AGC, or HCC with c-Met gene amplification ≥ 5 copies, or c-Met protein overexpression (IHC 3+). HCC subjects must have Child Pugh Class A.
5. Available fresh samples of NSCLC (except for c-Met exon 14 skipping mutation that can be from archival tumor sample), and available fresh or archival tumor sample of AGC and HCC for c-Met gene alteration characterization or determination of c-Met protein overexpression (IHC 3+). Fine needle aspiration and cytology samples are not sufficient.
6. In Phase Ia/Ib, all NSCLC subjects with EGFR mutation must have progressive disease after 1 or 2 lines of prior therapy including at least an EGFR-TKI targeting other than c-Met alterations. Subjects with c-Met exon 14 skipping mutation must have received at least 1 line of standard therapy in Phase Ia and can be first or second line subjects in Phase Ib. In Phase Ib, subjects with AGC must have progressive disease after at least 1 line of prior standard therapy and subjects with HCC must have received 1 line of targeted agent therapy.
7. At least 1 measurable target lesion.
8. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
9. Adequate organ function as documented
10. Toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade 0 or 1 as per the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), excluding alopecia.

Exclusion Criteria:

1. Pregnant (serum human chorionic gonadotropin positive) or breastfeeding female subject.
2. Prior anti-tumor systemic chemotherapy or loco-regional therapy for HCC (such as percutaneous ethanol injection, chemoembolization or radiofrequency ablation), biologics therapy, Chinese herbal anti-cancer or anti-infective medication within 28 days or 5 × half life time, whichever occurs last, before the first dose.
3. Prior therapy with another c-Met inhibitor.
4. Presence of EGFR T790M mutation in NSCLC subjects pretreated with an EGFR-TKI; Known KRAS/ALK/ROS1 mutation/rearrangement in NSCLC subjects with c-Met exon 14 skipping mutation.
5. Known or suspected hypersensitivity to SCC244 and/or its excipients.
6. Palliative radiotherapy to bone metastasis within 4 weeks prior to the first dosing.
7. Prior or concomitant other malignant tumor (except effectively controlled non-melanoma skin cancer, breast carcinoma in situ or cervix cancer in situ and superficial bladder cancer within past 5 years).
8. Cardiac function impairment or clinically significant heart disease including congestive heart-failure ≥ Grade 2 according to grading of New York Heart Association, arrhythmia, conduction abnormality requiring treatment, myocardium diseases or uncontrollable hypertension within 6 months prior to screening. QTc-prolongation > 470 msec, risk factors for Torsades De Pointe, hypokalemia or family history of long-QT-Syndrome.
9. History of stroke within 6 months prior to screening.
10. Known central nervous system or brain metastasis that is either symptomatic or untreated. Metastases that have been treated by complete resection and/or radiotherapy demonstrating stability or improvement are not an exclusion criterion provided they are stable as shown by CT scan for at least 1 month without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants.
11. Inability to swallow oral medication, or active digestive system disease, or major digestive surgery, which in the Investigator's opinion can affect administration and absorption of SCC244 (such as active ulcerative disease, uncontrollable diarrhea, and small bowel resection).
12. Any disease or condition with clinical significance (such as pancreatitis, uncontrollable diabetes, active or uncontrollable infection, drug or alcohol abuse, or psychiatric conditions), which can affect protocol compliance.
13. Positive result for active infection by hepatitis B or C virus (HBV or HCV); known positivity for human immunodeficiency virus (HIV) infection.
14. Men and women of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy until the end of trial.

Contacts and Locations

Contacts

Contact: Yilong Wu, M.D.; +86-20-83827812*21187; syylwu@live.cn

Locations

China, Guangzhou

Guangdong General Hospital; Recruiting

Guangzhou, Guangzhou, China, 510080

Contact: Yilong Wu, MD +86-20-83827812*21187 syylwu@live.cn

Principal Investigator: Yilong Wu, MD

Sponsors and Collaborators

Haihe Biopharma Co., Ltd.

Investigators

• Principal Investigator: Yilong Wu, M.D.; Guangdong Provincial People's Hospital

More Information

• Responsible Party: Haihe Biopharma Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03466268
• Other Study ID Numbers: SCC244-101
• First Posted: March 15, 2018
• Last Update Posted: March 11, 2020
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Haihe Biopharma Co., Ltd.:

Safety; Tolerability; Pharmacokinetics; Anti-tumor activity

Additional relevant MeSH terms:

Neoplasms