Inclusion Criteria:
1. Informed consent signed by the subject prior to conducting study-specific
procedures.
2. Male or female subjects ≥ 18 years of age.
3. Histological diagnosis as follows:
1. Parts A and B (Cohorts A1, A2, and B1): subjects must have a histological
diagnosis of any type of carcinoma, sarcoma, or melanoma with progressive
metastatic disease, or progressive locally advanced disease not amenable to
local therapy with curative intent.
2. Part B (Expansion Cohorts B2-B3): subjects must have a histological diagnosis
of the relevant tumor type (CSCC or PROC) with advanced/metastatic disease not
amenable to local therapy with curative intent.
4. Prior therapies:
a. Part A (dose-escalation) and Cohort B1 (monotherapy expansion) i. Subjects must
have experienced progressive disease (PD) on an established standard systemic
anti-cancer therapy for a given tumor type or have been intolerant to such therapy,
or in the opinion of the Investigator have been considered ineligible for a
particular form of standard therapy on medical grounds. Subjects must have no
available proven curative or life prolonging therapies.
b. Cohorts B4 and B5 (mini-expansion cohorts) i. Subjects must have received a
PD-(L)1 inhibitor-based therapy, either alone or in combination with other
anti-cancer agents, for at least 12 weeks. If subjects have received other lines of
immunotherapy, including PD-(L)1-based therapy, they must have demonstrated clinical
benefit on each prior immunotherapy. Subjects may also have received additional
anti-cancer therapies after failure of a PD-(L)1 inhibitor, but 2nd line subjects
are preferred.
c. Cohorts B2 and B3 (dose-expansion) i. Cohort B2 subjects (CSCC) must have
received a PD-(L)1 inhibitor. Subjects may not have received an additional
immunotherapy.
ii. Cohort B3 subjects (PROC) must have received platinum-based therapy and
experienced disease progression on or within 6 months of completion of such therapy.
Subjects may have received prior anti-PD-1 therapy. Subjects may have received
additional therapies after failure of platinum-based therapy.
5. Subjects must have measurable disease per RECIST v1.1.
6. People of childbearing potential, if not postmenopausal (defined as no menses for at
least 12 continuous months prior to study entry) or surgically sterile, must be
willing to practice at least one of the highly effective methods of birth control
described in Section 4.3 for at least a menstrual cycle (or partner's menstrual
cycle, for male subjects) before and for 4 months after study medication
administration.
7. Resolution of prior clinically significant therapy-related AEs (excluding alopecia
and ≤ Grade 2 peripheral neuropathy) to ≤ Grade 1 per NCI-CTCAE version 5.0, and no
treatment for these AEs for at least 2 weeks prior to the time of enrollment.
Electrolyte and hormonal supplementation may be used to treat these AEs provided the
subject is stable on these supplements.
8. Minimum of 2 weeks since the last dose of other hormone therapy and 3 weeks since
the last dose of other systemic cancer therapy or radiotherapy (> 4 weeks in case of
nitrosoureas or radio-immuno conjugate therapy). Adjuvant hormonal therapy (e.g.,
tamoxifen) is allowed provided the original tumor diagnosis was more than 3 years
before the first dose of study medication. Subjects with prostate cancer on stable
doses of anti-hormone treatment may remain on therapy for this trial.
9. Subjects must have adequate organ function.
10. Biopsy specimens:
1. All subjects must be able to supply an archival tumor tissue specimen. If an
archival specimen is not available, subjects may remain eligible with approval
of the medical monitor.
2. Subjects in Cohort B1 must consent to pre- and on-treatment biopsies. Tissue
obtained for the biopsy must not be previously irradiated. No systemic
anti-neoplastic therapy may be received by the subject between the time of the
biopsy and the first administration of study medication.
3. Subjects in all other cohorts will be asked to consent to pre- and on-treatment
biopsies for biomarker analysis of the acquired tissue. These biopsies are
optional and not required for study participation. Tissue obtained for the
biopsy must not be previously irradiated. No systemic anti-neoplastic therapy
may be received by the subject between the time of the biopsy and the first
administration of study medication.
11. Subject is able and willing to comply with the protocol and the restrictions and
assessments therein.
12. As required by local regulations or law, subjects must fulfill the obligation of
affiliation or beneficiary of a social security or similar scheme.
Exclusion Criteria:
1. Subject previously had a severe hypersensitivity reaction to treatment with another
monoclonal antibody (mAb).
2. Life expectancy < 12 weeks.
3. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) >
2.
4. Prior organ or stem cell transplant.
5. Subjects with symptomatic ascites or pleural effusion. Subjects who are clinically
stable for at least 2 weeks following treatment for these conditions (including
therapeutic thoraco- or paracentesis) are eligible.
6. Subject has a known active central nervous system (CNS) primary tumor or metastases
and/or carcinomatous meningitis. Subjects with previously treated brain metastases
may participate provided they are clinically stable for at least 4 weeks prior to
study entry, have no radiological evidence of new or enlarging brain metastases, and
are off steroids or on a stable dose up to an equivalent of prednisone 10 mg/day for
at least 15 days prior to first dose of study medication. Subjects who have symptoms
consistent with CNS metastasis must have a negative magnetic resonance imaging (MRI)
scan during the screening period.
7. Subject has a known history of a hematologic malignancy, malignant primary brain
tumor, or another malignant primary solid tumor (other than that under study),
unless the subject has undergone potentially curative therapy with no evidence of
recurrent disease for at least 3 years before the start of treatment.
1. Subjects with a known history of AJCC Stage 1 cancer that has undergone
potentially curative therapy with no evidence of recurrent disease for at least
1 year before the start of treatment may be eligible at the Investigator's
discretion after consultation with the Sponsor.
2. Subjects who underwent successful definitive resection of basal cell carcinoma
of the skin, superficial bladder cancer, squamous cell carcinoma of the skin,
in situ cervical cancer, or other in situ cancers at any time before the start
of treatment, and have no evidence of recurrent disease, are eligible.
8. Recent or ongoing serious infection including the following:
1. Any uncontrolled Grade 3 or higher (per NCI-CTCAE version 5.0) viral,
bacterial, or fungal infection within 2 weeks prior to the first dose of OR502.
Routine antimicrobial prophylaxis is allowed.
2. Uncontrolled infection with human immunodeficiency virus (HIV). Subjects on
stable highly active antiretroviral therapy (HAART) with undetectable viral
load and normal CD4 counts for at least 6 months prior to study entry are
eligible. Serological testing for HIV at screening is not required.
3. Known to be positive for hepatitis B virus (HBV) surface antigen, or any other
positive test for hepatitis B indicating acute or chronic infection. Subjects
who are or have received anti-HBV therapy and have undetectable HBV DNA for at
least 6 months prior to study entry are eligible. Serological testing for
hepatitis B at screening is not required.
4. Known active hepatitis C as determined by positive serology and confirmed by
polymerase chain reaction (PCR). Subjects on or having received anti-retroviral
therapy are eligible provided they are virus-free by PCR for at least 6 months
prior to study entry. Serological testing for hepatitis C at screening is not
required.
5. Known active or latent tuberculosis (testing at screening is not required).
9. Autoimmune disease or inflammatory condition requiring systemic anti-inflammatory
therapy with exceptions as noted in Exclusion Criterion 10. Subjects on hormone
replacement therapy for autoimmune-induced endocrinopathies are eligible.
10. Use of systemic corticosteroids within 15 days or other immunosuppressive drugs
within 30 days prior to start of the study, with the exception of corticosteroids as
replacement therapy up to an equivalent of prednisone 10 mg/day, which are allowed.
11. QTc interval ≥ 470 msec by electrocardiogram (ECG).
12. Subject has received an investigational product or been treated with an
investigational device within 30 days prior to first administration of study
medication.
13. Subject has received a live vaccine within 30 days prior to first administration of
study medication.
14. For Cohorts A2, B1, B2, and B3 only:
1. Known hypersensitivity to cemiplimab or any of its excipients or
contraindicated to cemiplimab per approved local labeling.
2. Interstitial lung disease.
3. Prior pneumonitis requiring systemic corticosteroid therapy.
4. Receiving immunosuppressive therapy, with exceptions as noted in Exclusion
Criterion 10.
5. A history of severe immune-related adverse reactions from treatment with
ipilimumab, defined as any Grade 4 toxicity or Grade 3 toxicity requiring
corticosteroid treatment (> 10 mg/day prednisone or equivalent) for more than
12 weeks.
15. Concurrent therapy with anti-cancer or anti-neoplastic drugs, with the exception of
adjuvant hormonal therapy, which is allowed as outlined in Inclusion Criterion 8.
16. History or clinical evidence of any surgical or medical condition that the
Investigator judges as likely to interfere with the results of the study or pose an
additional risk in participating, e.g., rapidly progressive or uncontrolled disease
involving a major organ system-vascular, cardiac, pulmonary, gastrointestinal,
gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, autoimmune or an
immunodeficiency, or clinically significant active psychiatric or abuse disorders.
17. Subjects who, at the time of signing informed consent, had a recent history (within
the last year) of chronic substance abuse.
18. Subject is pregnant or breastfeeding or expecting to conceive or father children
within the projected duration of the study.
19. Vulnerable persons: subjects under judicial safeguard, subjects deprived of their
liberty by judicial or administrative decision, subjects under psychiatric care
without their consent, subjects admitted to a health or social institution for
purposes other than research, adults subject to a measure of legal protection
(guardianship or curatorship), and subjects unable to express their consent.
