A Study of KM257 in Patients With Advanced HER2-positive or Expressing Solid Tumors.

Advanced Solid Tumor Clinical Trial

Official title:

The Safety, Tolerability, Pharmacokinetic Characteristics and Efficacy of KM257 in Patients With Advanced HER2-positive or Expressing Solid Tumors in a Single-arm, Open-label, Multi-center Phase 1 Clinical Study.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05320874
• Other study ID #: KM257-1001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 2022
• Est. completion date: November 2026

Study information

• Verified date: April 2022
• Source: Xuanzhu Biopharmaceutical Co., Ltd.
• Contact: Xingming Fan
• Phone: 0086-18513114991
• Email: fanxingming[@]xuanzhubio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a first-in-human, 2-part study to investigate the safety, tolerability, pharmacokinetics and efficacy of KM257 by itself and combined with selected chemotherapy agents in patients with advanced HER2-positive or expressing cancers.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 232
• Est. completion date: November 2026
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Able to understand, voluntarily participate and willing to sign the ICF.

2. Male or female subject >= 18 years and =<75 years.

3. Histologically or cytologically confirmed advanced solid tumors.

4. HER2 positive or expressing.

5. ECOG score 0 or 1.

6. According to the definition of RECIST1.1, for Part1a, the patient has evaluable but Non-measurable lesion can be accepted. For Part1b, the patient has at least one measurable lesion.

7. Life expectancy=12weeks.

8. Adequate organ function.

9. Subjects (women of child-bearing potential and males with fertile female partner) must be willing to use viable contraception method.

Exclusion Criteria:

1. primary CNS tumors (including meningeal tumors), symptomatic or untreated CNS metastases(including meningeal metastases).

2. Subjects who had other malignancies in the 2 years prior to the first administration of the investigational drug were excluded in Phase Ib, except those who had basal cell carcinoma, breast cancer in situ, or cervical cancer in situ and had no recurrence and metastasis after radical therapy.

3. Accepted any other anti-tumor drug therapies within 2 weeks before first dose.

4. Accepted major surgery or radical radiotherapy within 4 weeks before first dose; Accepted palliative radiotherapy within 2 weeks before first dose; Accepted radioactive agents(strontium, samarium, etc.)for therapeutic purposes within 8 weeks before first dose.

5. Participating in other studies involving investigational drug(s) = 4 weeks before the first dose of KM257.

6. Subjects with interstitial lung disease or non-infectious pneumonia and related history.

7. Infection with HIV disease.

8. Active hepatitis.

9. Had an active infection requiring systemic treatment within 2 weeks prior to initial administration of the investigational drug.

10. Cavity effusion (pleural effusion, ascites, pericardial effusion, etc.) are not well controlled. Subjects are eligible with clinically controlled and stable neurologic function >= 4 weeks, which is no evidence of CNS disease progression; Subjects with

11. Subjects who have received organ transplants.

12. Unresolved toxicities ( Common Terminology Criteria for Adverse Event (CTCAE, version 5), grade greater than or equal to2) from prior anti-cancer therapy. (with the exception of alopecia, the special provisions of inclusion criteria);

13. Subjects who have a history of severe allergic reactions to antibody medications or have a history of severe allergic asthma (CTCAE V5.0 grade =3).

14. Subjects with a known history of alcohol or drug abuse.

15. History of myocardial infarction or unstable angina within 6 months prior to enrollment, congestive heart failure (NYHA Class=2), or clinically significant cardiac disease,LVEF<50%,QTc Fridericia (QTcF) > 470 ms for female, QTc Fridericia (QTcF) > 450 ms for male.

16. History of TIA or stroke within 6 months prior to initial administration of KM257.

17. Subjects known to have a mental illness that may affect trial compliance.

18. The investigator considers that the subject has any clinical or laboratory abnormalities or other reasons that would disqualify him or her from participating in this clinical study.

19. Part1b cohort 2: subjects with known mutations in exons 2, 3, and 4 of KRAS/NRAS and in V600E of BRAF.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Biological:
• KM257 Bispecific antibody
Part 1a dose escalation: There will be 3 increasing dose levels (3mg/kg,6mg/kg,12mg/kg). Patients will be intravenously administrated with one dose of KM257, QW for continuous cycles of 21 consecutive days for each cycle. The dosing interval may be adjusted during the study based on emerging data from this trial. Part 1b dose expansion: Part1b:For cohort 1 and cohort2, KM257 will be given at the RP2D identified in Part1a; For cohort 3 to 7:KM257 will be given combined with one of the following selected drug combination: Drug: Capecitabine Combination therapy with KM257 - Cohort 3 Drug: Paclitaxel or Docetaxel or Irinotecan Combination therapy with KM257 - Cohort 4 Drug: Gemcitabine+Cisplatin Combination therapy with KM257 - Cohort 5 Drug: Gemcitabine+Cisplatin or Carboplatin Combination therapy with KM257 - Cohort 6 Drug:Carboplatin+Paclitaxel Combination therapy with KM257 - Cohort 7

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Xuanzhu Biopharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) (Part 1a)	Determine maximum tolerated dose (MTD) of KM257.	Up to 3 weeks
Primary	Recommended phase 2 dose (RP2D) (if has) (Part 1a)	Determine recommended phase 2 dose (RP2D) of KM257.	Up to 3 weeks
Primary	Number of patients with adverse events.(Part 1a)	Number of patients who experienced an adverse event	Up to 8 months.
Primary	Objective response rate (ORR) (Part 1b)	Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 2-3 years.
Secondary	Area under the concentration versus time curve of KM257 in plasma (AUC) (Part 1a and Part1b).	To determine the AUC of KM257.	Up to 8 months for Part 1a; Up to 2 to 3 years for Part1b.
Secondary	Maximum serum concentration (Cmax) of KM257(Part 1a and Part 1b ).	To determine the maximum serum concentration (Cmax) of KM257.	Up to 63days for Part 1a; Up to 63 days for Part1b.
Secondary	Time of Maximum observed serum concentration (Tmax) of KM257 (Part1 and Part1b ) .	To determine the Tmax of KM257.	Up to 63days for Part 1a; Up to 63days for Part1b.
Secondary	Serum Half-life (T-HALF) of KM257. (Part1a and Part1b)	To determine the t1/2 of KM257.	Up to 63days.
Secondary	Frequency and titer of anti-KM257 antibody. (Part1a and Part1b)	To determine the immunogenicity of KM257.	up to 8months for Part1a and up to 2-3 years for Part1b.
Secondary	Objective response rate (ORR) (Part 1a)	Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 8months.
Secondary	Progression free survival (PFS) (Part 1a and Part 1b)	To determine the PFS by investigator.	up to 2-3 years.
Secondary	Disease control rate (DCR) (Part 1a and Part 1b)	To determine the DCR by investigator.	up to 2-3 years.
Secondary	Overall survival (OS) (Part1a and Part1b )	To determine the OS by investigator.	up to 2-3 years.
Secondary	Number of patients with adverse events (Phase 1b)	Incidence of AE as assessed by CTCAE 5.0	up to 2-3 years.