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

NCT05320874 | Not Yet Recruiting Phase 1

• 1 other identifier: KM257-1001
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 1

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

Keywords

KM257; Safety, tolerability, pharmacokinetics and efficacy; Advanced HER2 positive or expressing solid tumors

Outcome Measures

Primary Outcomes (4)

• Maximum tolerated dose (MTD) (Part 1a)

  Determine maximum tolerated dose (MTD) of KM257.

  Up to 3 weeks

• Recommended phase 2 dose (RP2D) (if has) (Part 1a)

  Determine recommended phase 2 dose (RP2D) of KM257.

  Up to 3 weeks

• Number of patients with adverse events.(Part 1a)

  Number of patients who experienced an adverse event

  Up to 8 months.

• 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 Outcomes (10)

• Area under the concentration versus time curve of KM257 in plasma (AUC) (Part 1a and Part1b).

  Up to 8 months for Part 1a; Up to 2 to 3 years for Part1b.

• Maximum serum concentration (Cmax) of KM257(Part 1a and Part 1b ).

  Up to 63days for Part 1a; Up to 63 days for Part1b.

• Time of Maximum observed serum concentration (Tmax) of KM257 (Part1 and Part1b ) .

  Up to 63days for Part 1a; Up to 63days for Part1b.

• Serum Half-life (T-HALF) of KM257. (Part1a and Part1b)

  Up to 63days.

• Frequency and titer of anti-KM257 antibody. (Part1a and Part1b)

  up to 8months for Part1a and up to 2-3 years for Part1b.

Study Arms (1)

KM257

EXPERIMENTAL

KM257 Bispecific antibody

Biological: KM257 Bispecific antibody

Interventions

KM257 Bispecific antibody 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

KM257

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand, voluntarily participate and willing to sign the ICF.
• Male or female subject \>= 18 years and =\<75 years.
• Histologically or cytologically confirmed advanced solid tumors.
• HER2 positive or expressing.
• ECOG score 0 or 1.
• 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.
• Life expectancy≥12weeks.
• Adequate organ function.
• Subjects (women of child-bearing potential and males with fertile female partner) must be willing to use viable contraception method.

You may not qualify if:

• primary CNS tumors (including meningeal tumors), symptomatic or untreated CNS metastases(including meningeal metastases).
• 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.
• Accepted any other anti-tumor drug therapies within 2 weeks before first dose.
• 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.
• Participating in other studies involving investigational drug(s) ≤ 4 weeks before the first dose of KM257.
• Subjects with interstitial lung disease or non-infectious pneumonia and related history.
• Infection with HIV disease.
• Active hepatitis.
• Had an active infection requiring systemic treatment within 2 weeks prior to initial administration of the investigational drug.
• 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
• Subjects who have received organ transplants.
• 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).
• Subjects with a known history of alcohol or drug abuse.
• 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.

Sponsors & Collaborators

• Xuanzhu Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Central Study Contacts

Xingming Fan

CONTACT

0086-18513114991; fanxingming@xuanzhubio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 11, 2022
• Study Start: April 1, 2022
• Primary Completion: June 1, 2024
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 11, 2022

Record last verified: 2022-04

Locations

CN (1)