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.

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.