| Eligibility |
INCLUSION CRITERIA:
Patients eligible for inclusion in this study must meet all of the following criteria:
1. Be willing and able to provide written informed consent for the trial.
2. Written informed consent must be obtained prior to any study procedures.
3. Age =18 years (or =16 years at Dana Farber Cancer Institute).
4. Histologically- or cytologically-confirmed relapsed/refractory metastatic or
locally-advanced solid tumor or lymphoma whose disease has progressed despite all
appropriate curative or life-prolonging treatments, are intolerant to these therapies
or have refused standard treatment.
1. Inclusion criteria: RPTR-147:1 (Arms A & B) treatment groups
Cohort enrollment may be limited to potentially immune-responsive tumor types
meeting the above criterion during the first approximately 2 weeks of the
enrollment period of each cohort due to their potential to respond to and
activate RPTR-147:1:
- NSCLC
- Melanoma
- Clear cell cancer of the kidney
- HNSCC
- Urothelial cancer
- Lymphoma
- Sarcomas
- Ovarian Cancer
- Based upon emerging data that will be discussed during the Safety Review
Committee meetings, the patient population may be further limited based
other factors
2. Inclusion criteria: RPTR-147:2 (Arm C) treatment group Patients with cancers
known to be HPV-16 positive.
5. Patient must have documented HLA-typing results that meet the study requirements. The
list of eligible HLA alleles will be updated on an ongoing basis by the Sponsor.
• Once sufficient data has been collected for drug product analytics, or sufficient
HLA coverage is obtained, the HLA-type eligibility requirement may be discontinued by
the Sponsor.
6. For patients with solid tumors, use Response Evaluation Criteria in Solid Tumor
(RECIST) v1.1: measurable disease (at least one measurable non-nodal lesion of at
least 1.0 cm in longest diameter or nodal lesion of at least 1.5 cm in shortest
diameter) documented within 10 weeks of their projected C1D1 visit.
For patients with lymphoma, use the Lugano classification: measurable disease defined
as at least one lesion that can be accurately measured in at least two dimensions with
spiral computed tomography (CT) scan documented within 10 weeks of their projected
C1D1 visit. Minimum measurement must be >15 mm in the longest diameter.
NOTE: If there are no pre-existing radiologic assessments within 10 weeks of the
projected C1D1 visit, other evidence of measurable disease may be considered
sufficient to fulfill this criterion following documented discussion and approval from
the Sponsor.
NOTE: Please note, for dosing/Screening Period 2, patients must have a radiological
assessment per mRECIST v1.1 (solid tumor) or Lugano classification (lymphomas) within
28 days before receiving treatment with RPTR-147 to serve as the patient's baseline
tumor assessment.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status =1.
8. Have provided archival tumor tissue sample or newly obtained core or excisional
biopsy, during screening period 2, of a tumor lesion not previously irradiated.
Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly
obtained biopsies are preferred to archived tissue. Further details can be found in
the Laboratory Manual.
Note: If submitting unstained cut slides, newly cut slides should be submitted to the
testing laboratory within 14 days from the date slides are cut.
9. RPTR-147:1 in combination with pembrolizumab (Arm B only) - Patients should have
malignancies for which the response rate to anti-PD1/PDL1 monotherapy is <20% or, if
they have malignancies for which anti-PD1/PDL1 are standard of care must have
progressed on treatment with an anti-PD1/L1 monoclonal antibody (mAb) administered
either as monotherapy, or in combination with other checkpoint inhibitors or other
therapies. PD-1 treatment progression is defined by meeting all of the following
criteria:
1. Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
2. Has demonstrated disease progression (PD) after PD-1/L1 as defined by RECIST
v1.1. The initial evidence of PD is to be confirmed by a second assessment no
less than four weeks from the date of the first documented PD, in the absence of
rapid clinical progression.
3. Progressive disease has been documented as per the following within 12 weeks from
the last dose of anti-PD-1/L1 mAb.
10. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP)
2. A WOCBP who agrees to follow contraceptive guidance during the treatment period
and for at least 120 days after the last dose of study treatment.
11. A male participant must agree to use contraception during the treatment period and for
at least 165 days after the last dose of study treatment.
EXCLUSION CRITERIA:
Patients eligible for this study must not meet any of the following criteria:
1. Previously identified hypersensitivity to components of RPTR-147 or excipients.
2. Pembrolizumab combination Arm B only - Has severe hypersensitivity (=Grade 3) to
pembrolizumab and/or any of its excipients.
3. Patients with T-cell lymphomas or small lymphocytic lymphoma.
4. Presence of active central nervous system (CNS) disease and/or carcinomatous
meningitis. Participants with previously treated brain metastases may participate
provided they are radiologically stable, i.e., without evidence of progression for at
least 4 weeks by repeat imaging (note that the repeat imaging should be performed
during study screening), clinically stable, and without requirement of steroid
treatment for at least 14 days prior to first dose of study treatment.
5. Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease. For any
interim radiotherapy received after the baseline tumor assessment, the target lesions
must not be irradiated.
6. Patient having out of range laboratory values defined as:
- Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) <40
mL/min
- Total bilirubin >1.5 x upper limit of normal (ULN), except for patients with
Gilbert's syndrome who are excluded if total bilirubin >3.0 x ULN or direct
bilirubin >1.5 x ULN
- Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) >3 x ULN,
except for patients that have tumor involvement of the liver, who are excluded if
ALT >5 x ULN
- Absolute neutrophil count =1.0 x 109/L
- =0.5 x 109/L and increasing following prior myelosuppressive treatment will be
eligible
- Screening Period 1 Only: Absolute lymphocyte count =1.0 x 109/L for solid tumor
patients or =7.0 x 108/L for lymphoma patients prior to the apheresis procedure.
- Platelet count =75 x 109/L absent platelet transfusion for 2 weeks
- Hemoglobin (Hgb) =9 g/dL absent RBC transfusion for 2 weeks
- =8 g/dL and increasing following prior myelosuppressive treatment will be
eligible
- Coagulation (prothrombin time [PT] or international normalized ratio [INR] and
partial thromboplastin time [PTT] or activated partial thromboplastin time
[aPTT])
- >1.5 × ULN unless participant is receiving anticoagulant therapy as long as
PT/INR and PTT/aPTT is within therapeutic range of intended use of anticoagulants
- Potassium, magnesium, calcium or phosphate abnormality > CTCAE v5.0 Grade 1
despite appropriate oral replacement therapy
- Screening Period 1 Only: Serum triglycerides >500 mg/dL due to potential
interference with cell separation methods
7. Impaired cardiac function or clinically significant cardiac disease, including any of
the following:
- Clinically significant and/or uncontrolled heart disease such as congestive heart
failure requiring treatment (New York Heart Association [NYHA] Grade =2),
uncontrolled hypertension, or clinically significant arrhythmia
- Acute myocardial infarction or unstable angina pectoris <6 months prior to study
entry
8. Patients with active, known or suspected autoimmune disease that has required systemic
treatment in the past 2 years (i.e., with use of disease modifying agents,
corticosteroids, or immunosuppressive drugs).
1. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a
form of systemic treatment and is allowed.
2. Patients with vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to
autoimmune condition only requiring hormone replacement, psoriasis not requiring
systemic treatment, or conditions not expected to recur in the absence of an
external trigger are permitted to enroll.
9. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
11. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that
have undergone potentially curative therapy are not excluded.
12. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is
required unless mandated by local health authority.
13. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local
health authority.
14. Malignant disease, other than that being treated in this study expected to interfere
with the assessment of efficacy in the opinion of the investigator.
15. Active infection requiring systemic therapy.
16. Patients requiring chronic treatment with systemic steroid therapy, other than
replacement dose steroids in the setting of adrenal insufficiency. Topical, inhaled,
nasal, or ophthalmic steroids are allowed.
17. Patients receiving systemic treatment with any immunosuppressive medication.
18. Use of any live vaccines against infectious diseases within 30 days of initiation of
study treatment. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever,
rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza
vaccines for injection are generally killed virus vaccines and are allowed; however,
intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are
not allowed.
19. Major surgery within 4 weeks of the first dose of study treatment (mediastinoscopy,
insertion of a central venous access device, and insertion of a feeding tube are not
considered major surgery).
Note: If participant received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting study
treatment.
20. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study treatment.
Note: Patients who have entered the follow-up phase of another investigational study
may participate in this study as long as it has been 4 weeks after the last dose of
the previous investigational agent.
Note: Patients may participate in other local biomarker studies following documented
discussion and approval from Repertoire Immune Medicines.
Note: T-cell imaging agents may be permitted following documented discussion and
approval with the Sponsor.
21. Presence of =CTCAE v5.0 Grade 2 toxicity from prior therapy (except alopecia,
peripheral neuropathy, and ototoxicity, which are excluded if =CTCAE v5.0 Grade 3) due
to prior cancer treatment.
22. Initiation of hematopoietic colony-stimulating growth factors (e.g. Granulocyte Colony
Stimulating Factor [G-CSF], Granulocyte Macrophage Colony Stimulating Factor [GMCSF],
Macrophage Colony Stimulating Factor [M-CSF]) =2 weeks prior to start of study drug.
An erythroid stimulating agent is allowed as long as it was initiated at least 2 weeks
prior to the first dose of study treatment.
23. An unresolved AE (must be =Grade 1 or the patient's baseline).
24. Prior treatment with CAR-T-cell therapy.
25. Has undergone prior allogeneic HSCT
26. RPTR-147 Monotherapy: Patients who were required to discontinue PD-1/PD-L1, CTLA-4, or
other immunomodulatory antibodies due to =Grade 3 irAE may be included following
discussion with the Sponsor.
27. RPTR-147:1 in Combination with pembrolizumab: Has received prior therapy with an
anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another
stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was
discontinued from that treatment due to a Grade 3 or higher irAE.
28. Patients with a history of >3 lines of chemotherapy in the metastatic setting may be
eligible for enrollment following discussion with the Sponsor.
29. Patients with a history of rapidly progressing disease on immunotherapy.
1. Prior clinical or radiological disease progression (excluding pseudoprogression)
within 8 weeks after starting prior immunotherapy with PD-1/PDL-1, CTLA-4
inhibitors.
2. These patients may only be enrolled following discussion with the Sponsor to
account for manufacturing time.
30. Prior therapy with PD-1/PDL-1, CTLA-4 or other immunomodulatory antibodies inhibitors:
1. =2 weeks prior to the apheresis procedure
2. =4 weeks prior to the first dose of study treatment
31. Systemic anti-cancer therapy within 5 half-lives or 2 weeks; whichever occurs first,
of the apheresis procedure and the first dose of study treatment.
1. Systemic cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and
nitrosoureas, =6 weeks prior to the first dose of study treatment
2. Participants must have recovered from all AEs due to previous therapies to =Grade
1 or baseline. Participants with =Grade 2 neuropathy may be eligible.
32. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator.
33. Has known psychiatric or substance abuse disorders that would interfere with
cooperating with the requirements of the study.
34. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 150 days
after the last dose of study treatment.
35. Women of childbearing potential (WOCBP), defined as all women physiologically capable
of becoming pregnant, unless they are using highly effective methods of contraception
during study treatment and for 120 days after the last dose of study treatment. Highly
effective contraception methods include:
1. Female sterilization, total hysterectomy, or tubal ligation at least 6 weeks
before taking study treatment.
2. Male sterilization (at least 6 months prior to screening). For female patients on
the study the vasectomized male partner should be the sole partner for that
patient.
3. Use of oral (estrogen and progesterone), injected or implanted combined hormonal
methods of contraception or placement of an intrauterine device (IUD) or
intrauterine system (IUS) or other forms of hormonal contraception that have
comparable efficacy (failure rate <1%), for example, hormone vaginal ring or
transdermal hormone contraception.
In case of use of oral contraception, women should have been stable on the same pill
for a minimum of 3 months before taking study treatment.
Women are considered post-menopausal and not of childbearing potential if they have
had 12 months of natural amenorrhea with an appropriate clinical profile or have had
surgical bilateral oophorectomy or tubal ligation at least 6 weeks prior to the first
dose of study treatment.
36. A WOCBP who has a positive urine pregnancy test (e.g. within 72 hours) prior to
treatment. If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.
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