Key Inclusion Criteria:

Subjects may be enrolled in this study only if they satisfy all the following criteria (NOTE: This is not an exhaustive list):

* Subjects aged ≥18 years.
* ECOG performance status ≤ 2
* Subjects with advanced relapsed, refractory, or resistant hematological malignancies, as defined below:

Part 1:

* Subjects with documented IDH mutation per local or institutional next generation sequence (NGS).
* Subjects must be refractory to or intolerant of established therapies.
* Subjects who have received prior IDH inhibitor treatment may be enrolled in the escalation phase.

Part 2:

* Subjects with documented IDH mutation of any of these subsets: IDH1 (R132C), IDH1 (R132H), IDH (R140Q), and IDH2 (R172K), including co-mutations and any combination thereof per local and institutional NGS.
* Patients must have received at least 1 prior line of therapy with an IDH inhibitor. An established standard of care with proven benefit for which the patient is eligible, must not be available at the time of enrollment.
* Patients with AML must not have standard therapeutic options available (including IDH inhibitors where approved) and have the following:

i. Relapsed AML unsuitable for intensive chemotherapy or venetoclax-based regimen or target agents; ii. Primary refractory AML unsuitable for intensive chemotherapy or venetoclax-based regimen or target agents.
* Patients with relapsed/refractory AML/HR-MDS/AITL include the following:
i. Relapsed AML unsuitable for intensive chemotherapy or venetoclax-based regimen or target agents
ii. Primary refractory AML unsuitable for intensive chemotherapy or venetoclax-based regimen or target agents.
iii. Relapsed/refractory AML that has progressed on prior IDH treatment

Key Exclusion Criteria:

Subjects are not eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):

* Subjects who received an investigational agent \<14 days prior to their first day of study drug administration.
* Subjects who are pregnant or breastfeeding.
* Subjects with an active severe infection, some treated infections and with an expected or with an unexplained fever \>38.3°C during screening visits or on their first day of study drug administration.
* Subjects with some current or prior heart conditions.
* Subjects taking medications that are known to prolong the QT interval may not be eligible.
* Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
* Some subjects with some current or prior gastrointestinal or liver diseases.
* Subjects with inadequate organ function as defined by the protocol.
* Subjects with a medical condition, physical examination finding, or clinical laboratory finding that, in the Investigators opinion, contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the subject at high risk from treatment complications.
* Subjects with a known hypersensitivity to HMPL-306 or to any of its excipients.
* Subjects with presence of second primary malignant tumors within the last 2 years, with the exception of the following, if medically controlled: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and carcinoma in situ of the breast.
* Part 2 Only: The time since the last dose of prior IDH inhibitor treatment is within 30 days prior to the first day of study drug administration