A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH
18 Years and older, Male and Female
An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and
preliminary efficacy of HMPL-306 in subjects with advanced relapsed, refractory, or resistant
hematological malignancies that harbor IDH mutations.
HMPL-306 is a dual IDH1/2 inhibitor
This is a phase 1, open-label, multicenter, single-arm study to evaluate safety,
tolerability, PK, PD, and preliminary efficacy of HMPL-306 administered orally in treatment
of subjects with advanced relapsed, refractory, or resistant hematological malignancies that
harbor IDH mutations (or co-mutations).
The study consists of 2 parts: a dose-escalation part (Part 1) and a dose-expansion part
(Part 2). The dose-escalation part will determine the MTD/R2PD. The dose-expansion part will
administer the MTD/RP2D to subjects with mIDH-positive hematological malignancies including,
but not limited to AML, HR-MDS, AITL.
- 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:
- Subjects with documented IDH mutation per local or institutional next generation
- Subjects must be refractory to or intolerant of established therapies.
- Subjects who have received prior IDH inhibitor treatment may be enrolled in the
- 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. An established standard
of care with proven benefit for which the patient is eligible, must not be available
at the time of enrollment.
- Subjects with MDS must have a Revised International Prognostic Scoring System (IPSS-R)
score of >4.5 (high and very high risk).
- 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. Subjects who relapse after transplantation; ii. Subjects in second or later
relapse; iii. Subjects who are refractory to initial induction or re-induction
- Subjects must not have progressed on prior IDH treatment unless isoform switching of
the IDH mutation has been documented following progression on the prior IDH inhibitor.
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
- Subjects with immediately life-threatening, severe complications of leukemia such as
uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated
- 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.
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials