A Study to Evaluate HH2853 in Patients with Relapsed/Refractory Non-Hodgkin's Lymphomas or Advanced Solid Tumors


About this study

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (how a drug moves within the body) and clinical activity of HH2853, an EZH1/2 Inhibitor, in patients with relapsed/refractory Non-Hodgkin's lymphomas or advanced solid tumors.


Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

1. Provided signed written informed consent prior to initiation of any study-related

2. Males and females ≥ 18years of age at the time of consent are obtained (or meet the
country's regulatory defined adult legal age);

3. Tumor type criteria:

1. Relapsed/refractory histologically documented non-Hodgkin's lymphoma (NHL) must
have received at least 2 prior systemic therapies (maximum <5 lines, patients
without treatment options available known to provide clinical benefit are also
eligible upon agreement from investigator and sponsor.) The specific requirements
for certain tumor types are listed below:

- Follicular lymphoma (FL) must meet criteria requiring at least two prior
systemic treatment per the GELF criteria and there is no salvage regimen
available (maximum <5 lines);

- Diffuse large B-cell lymphoma NOS (2016 WHO classification of lymphoma
neoplasms) relapsed or refractory with at least 2 prior regimen (e.g., at
least one regimen of anti-CD20 based therapy, maximum <5 lines) and not a
candidate for salvage regimens or autologous or allogeneic stem cell

- Relapsed/refractory clinicopathologically documented PTCL with at least 1
line of prior systemic treatment (maximum <5 lines). Subtypes include
Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS),
Angioimmunoblastic T-cell lymphoma (AITL), ALK+ Anaplastic large cell
lymphoma, anaplastic lymphoma kinase positive (ALCL), ALK-ALCL, Extranodal
natural killer (NK)/T-cell lymphoma-nasal type (ENKL),
Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic
intestinal T-cell lymphoma (MEITL), Hepatosplenic T-cell lymphoma (HSTCL),
Follicular T-cell lymphoma (FTCL), Nodal peripheral T-cell lymphoma with TFH
phenotype (PTCL-TFH) and other invasive T-cell-derived NHL that the
investigator considered eligible and approved by the sponsor (Other than
highly invasive subtype).

The definition of relapse: A relapse after CR or progression after PR with at
least one prior systemic therapy.

The definition of refractory: Tumor evaluation of PD after 2 cycles of treatment;
tumor evaluation of SD after 4 cycles of treatment; no response or treatment
progression within 1 month after completion of initial treatment; tumor
evaluation of PR but require second-line treatment immediately at the physician's

2. Solid tumors that meet the following criteria:

1. Histologically or cytologically documented advanced recurrent or metastatic
solid tumor.

2. Phase I dose escalation: Measurable or evaluable lesions by RECIST v1.1 in
at least 1 site; phase I dose extension and phase II: Measurable target
lesions by RECIST v1.1 in at least 1 site. (Lesions that have been treated
with radiotherapy or other local treatment are generally considered
unmeasurable unless there is definite progression of the lesion.)

3. Patients must have disease not amenable to surgery, radiation, or combined
modality therapy with curative intent. One of the following criteria should
be met.

- Patients must experience at least one prior standard therapy. Disease
progression occurred on or after last line of therapy, or intolerant to
last line of therapy (maximum ≤3 lines, Patients without treatment
options available known to provide clinical benefit are also eligible
upon agreement from investigator and sponsor)

- There is no approved therapy, or for which standard therapy is
unsuitable or refused by patients after being fully informed.

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1;

5. Availability of archival tissue within three years, or willingness to undergo fresh
biopsy if archival tissue is not available (only for phase I dose extension and phase
II) ;

6. Relapsed/Refractory FL, Epithelioid sarcoma, relapsed/refractory PTCL, other
relapsed/refractory non-Hodgkin's lymphomas with EZH2 mutation, and advanced solid
tumors with specific genetic alterations, including EZH2 mutation, INI1 deficiency,
BAP1 deficiency, ARID1A mutation, or/and SMARCA4 mutation tested by local labs will be
enrolled in phase I dose extension and phase II. For phase II, patients may be
enrolled in one of 3 cohorts upon their tumor types:

- Relapsed/Refractory FL

- Epithelioid sarcoma

- Relapsed/Refractory PTCL, other relapsed/refractory Non-Hodgkin's lymphomas with
EZH2 mutation, or advanced solid tumors with specific genetic alterations,
including EZH2 mutation, INI1 deficiency, BAP1 deficiency, ARID1A mutation,
or/and SMARCA4 mutation.

7. Predicted life expectancy of ≥ 3 months;

8. Patient must meet the following laboratory values:

1. Serum total Bilirubin ≤ 1.5 x ULN or ≤ 3.0 mg/dL for patients with Gilbert's

2. AST/SGOT and ALT/SGPT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present

3. 24-hour creatinine clearance (calculated* or measured value**)≥ 50 mL/min

*For calculated creatinine clearance (Ccr) value, the eligibility should be
determined using the Cockcroft-Gault formula:

1. Male Ccr (mL/mim) = body weight (kg) x (140-age)/[72 x creatinine (mg/dL)]

2. Female Ccr (mL/min) = male Ccr x 0.85 ** A measured value Ccr value (i.e.
not calculated) should meet this criterion.

4. Platelets ≥ 1 x LLN (no Platelet transfusion for 7 days prior to screening)

5. Hemoglobin (Hgb) ≥ 9 g/dL (no RBC transfusion for 7 days prior to screening)

6. Absolute Neutrophil Count (ANC) ≥ 1.0 x 10^9/L

7. Adequate coagulation function: International normalized ratio (INR) <1.3 (or <3.0
on anticoagulants)

Exclusion Criteria:

1. Any cancer-directed therapy (chemotherapy, antibody therapy, radiotherapy, hormonal
therapy, biologic or immunotherapy, Chinese medicine/Chinese patent medicine with
anti-tumor effect, etc.) within 28 days or five half-lives prior to first dose
(whichever is shorter); Small molecule anticancer therapy within 2 weeks or five
half-lives (whichever is longer); Local radiotherapy (without radioactive particle
implantation) within 14 days of first dose.

2. Symptomatic CNS metastases that are neurologically unstable or requiring increasing
doses of steroids to control CNS disease. Note: Any major surgery, radiotherapy or
immunotherapy within the 4 weeks prior to first dose of study drug, or palliative
radiotherapy to a single symptomatic lesion within the 2 weeks prior to first dose of
study drugs;

3. Patients with prior transplant are excluded; however, patients who have previously
received an autologous stem cell transplant are allowed if a minimum of 100 days has
elapsed from the time of transplant and the patient has recovered from
transplant-associated toxicities prior to the first dose of HH2853. Patients who have
previously received an allogeneic stem cell transplant are also allowed if a minimum
of 6 months has elapsed prior to the first dose of HH2853;

4. Major surgery within 4 weeks prior to first dose;

5. Current use of a prohibited medication or expected to require any of these medications
during treatment with study drug;

6. HIV (human immunodeficiency virus) infection, active hepatitis B or hepatitis C
patients (HBsAg positive patients with HBV (hepatitis B virus) DNA ≥ 10^3 copies or ≥
200 IU/mL; HCV antibody test results are positive, and HCV (hepatitis C virus) RNA PCR
test results are positive). However, patients that can be controlled with treatment
are eligible;

7. Concomitant malignancies or previous malignancies with less than 2 years of
disease-free interval at the time of enrollment (but basal cell carcinoma skin cancer,
cervical CIS (carcinoma in situ), CIS of the breast, localized or low Gleason grade
prostate cancer, and < T2 bladder cancer can be included);

8. Concurrent use of therapeutic warfarin is allowed. However, anticoagulants that do not
have reversal agents available are prohibited except low molecular weight heparin and
direct oral anticoagulants.

9. Any toxicities from prior treatment that have not recovered to ≤ CTCAE Grade 1 before
the start of study drug, with exception of hair loss or fatigue;

a) Lymphoma patients with ≤ Grade 3 lymphopenia can be enrolled at the discretion of
the investigator

10. Packed red blood cell or platelet transfusion within 7 days of screening laboratory

11. Gastrointestinal condition which could impair absorption of study medication;

12. Psychological, familial, sociological or geographical conditions that do not permit
compliance with the protocol;

13. Cardiac exclusion criteria:

1. History of acute coronary syndromes (including myocardial infarction and unstable
angina), coronary angioplasty, or stenting within the past 3 months prior to
first dose of study drug;

2. Fridericia's corrected QT interval (QTcF) > 450 ms (for male) and > 470 ms (for
female) on ECG conducted during screening;

3. Congenital long QT syndrome, or any known history of torsade de pointes (TdP), or
family history of unexplained sudden death;

4. History or current evidence of serious uncontrolled ventricular arrhythmias;

5. Symptomatic congestive heart failure (Class III or IV heart failure as defined by
the New York Heart Association (NYHA) functional classification system) within
the previous 3 months;

6. Left ventricular ejection fraction (LVEF) < 50%;

14. Any evidence of serious active infections requiring antibiotics;

15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study drug or their excipients;

16. Pregnant or breast-feeding female;

17. Contraception:

Patients who do not meet the following requirements will be excluded:

- For women: negative pregnancy test for females of child-bearing potential; must
be surgically sterile, postmenopausal (defined as no menstrual cycle for at least
12 consecutive months), or compliant with an acceptable contraceptive regimen (2
highly effective forms, such as oral contraceptives, condom with spermicide,
etc.) during and for 3 months after the treatment period. Abstinence is not
considered as an adequate contraceptive regimen;

- For men: must be surgically sterile, or compliant with a contraceptive regimen
(as above) during and for a minimum of 3 months after the treatment period.

18. Other serious illness or medical conditions at the Investigator's discretion, that may
influence study results, including but not limited to cerebrovascular diseases or lung

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/12/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Patrick Johnston, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Javier Munoz, M.D., M.B.A.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Han Tun, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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