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

NCT ID: NCT05320874

Last Updated: 2022-04-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 232 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-30
• Study Completion Date: 2026-11-30

Brief 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.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

KM257

KM257 Bispecific antibody

Group Type: EXPERIMENTAL

KM257 Bispecific antibody

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xuanzhu Biopharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Xingming Fan

Role: CONTACT

fanxingming@xuanzhubio.com

0086-18513114991

Facility Contacts

Lin Shen, Professor

Role: primary

doctorshenlin@sina.cn

0086-10-88196561

Other Identifiers

KM257-1001

Identifier Type: -

Identifier Source: org_study_id