Inclusion Criteria:
1. Informed consent signed by the subject prior to conducting study-specific
procedures.
2. Male or female subjects ≥ 18 and ≤ 100 years of age.
3. Histological diagnosis as follows:
1. Part A (dose-escalation Cohorts A1-A3): histological diagnosis of any type of
carcinoma, sarcoma, or melanoma with progressive metastatic disease, or
progressive locally advanced disease not amenable to local therapy.
2. Part B (expansion Cohorts B1-B3): histological diagnosis of the relevant tumor
type (NSCLC or melanoma) with advanced/metastatic disease not amenable to local
therapy.
a. Part C (biology cohort): histological or cytological diagnosis of any type of
carcinoma, sarcoma, or melanoma with progressive metastatic disease, or progressive
locally advanced disease not amenable to local therapy. At least 10 subjects each
must have a diagnosis of SCCHN, dedifferentiated liposarcoma, or leiomyosarcoma with
prior treatment described below.
4. Prior therapies:
a. Part A (dose-escalation) i. Subjects must have experienced 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. Part B (dose-expansion) i. Part B1 subjects (NSCLC) must have received
platinum-based therapy, unless contraindicated, and a PD-1 or PD-L1 inhibitor.
Subjects eligible for targeted therapies to EGFR, ALK, ROS, RET or NTRK (e.g.,
crizotinib) must have previously received and exhausted such therapies. Prior
therapies may have been administered alone or in combination. Subjects must have
received prior PD-(L)1-based therapy as the most recent prior therapy and
demonstrated progression while on that therapy.
ii. Part B2 subjects (NSCLC) must have received platinum-based therapy and a PD-1 or
PD-L1 inhibitor unless contraindicated. Subjects eligible targeted therapies to
EGFR, ALK, ROS, RET or NTRK (e.g., crizotinib) must have exhausted such therapies.
Prior therapies may have been administered alone or in combination. Part B2 subjects
may have received a total of 3 lines of prior therapy and are not required to have
received a PD-(L)1-based therapy as the most recent therapy.
iii. For melanoma: subjects must have received a PD-1 inhibitor, alone or in
combination with another immunotherapy. Eligible subjects may have received BRAF-
and MEK-targeted therapies. Subjects must have received prior PD-1-based therapy as
the most recent therapy and demonstrated radiographic progression while on that
therapy.
c. Part C (biology cohort): subjects other than those with liposarcoma,
leiomyosarcoma, or SCCHN must have experienced PD on an established standard medical
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 and must have no available
demonstrated curative or life-prolonging therapies. Subjects with liposarcoma must
have dedifferentiated liposarcoma, have received at least 1 prior systemic therapy,
and require additional treatment. For leiomyosarcoma, subjects must have received at
least 1 prior therapy for advanced or metastatic disease. For SCCHN, subjects must
have received 1 prior line of chemotherapy and a PD-1- or PD-L1-targeted agent alone
or in combination with chemotherapy unless contraindicated. No more than 2
chemotherapy regimens in the advanced setting for SCCHN are allowed. All subjects
must have demonstrated progression on the most recent line of therapy.
5. Subjects must have measurable disease per RECIST v1.1. Subjects in Part C must have
at least one 1 lesion amenable to biopsy and that is not to be used for response
assessment per RECIST v1.1.
6. If not postmenopausal or surgically sterile, subjects must be willing to practice at
least one of the following highly effective methods of birth control for at least a
menstrual cycle (or partner's menstrual cycle, for male subjects) before and for 3
months after study medication administration:
- (1) true abstinence, when this is in
line with the preferred and usual lifestyle of the subject, from sexual intercourse
with a member of the opposite sex; (2) sexual intercourse with vasectomized
male/sterilized female partner; (3) hormonal female contraceptive (oral, parenteral,
intravaginal, implantable, or transdermal) for at least 3 consecutive months prior
to investigational product administration (when not clinically contraindicated as in
breast, ovarian, and endometrial cancers); (4) use of an intrauterine contraceptive
device or intrauterine hormone-releasing system.
7. Resolution of prior-therapy-related AEs (excluding alopecia and grade ≤ 2 peripheral
neuropathy) to ≤ grade 1 per CTCAE v5.0, 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 (for
example tamoxifen) is allowed provided the original tumor diagnosis was more than 3
years before the first dose of study medication.
9. Subjects must have adequate organ function.
10. All subjects must be able to supply an archival tumor biopsy specimen. For Part C
(biology cohort), subjects must consent to a newly obtained tumor biopsy (that can
be biopsied based on Investigator's assessment) and to providing the acquired tissue
for biomarker analysis. An additional on-treatment biopsy is required for subjects
in Part C.
11. Subject is able and willing to comply with the protocol and the restrictions and
assessments therein.
Exclusion Criteria:
1. Subject previously had a severe hypersensitivity reaction to treatment with another
mAb.
2. Subject has ECOG PS > 2.
3. Life expectancy <12 weeks.
4. Prior organ or stem cell transplant.
5. Subjects with symptomatic ascites or pleural effusion.
6. Subject has a known active 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 MRI during in 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
that disease for at least 3 years.
8. Recent or ongoing serious infection including the following:
1. Any uncontrolled grade 3 or higher (per CTCAE v5.0) viral, bacterial, or fungal
infection within 2 weeks prior to the first dose of OR2805. Routine
antimicrobial prophylaxis is allowed.
2. Uncontrolled infection with HIV. Subjects on stable HARRT therapy 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 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.
4. Known active hepatitis C as determined by positive serology and confirmed by
PCR. Subjects on or having received antiretroviral therapy are eligible
provided they are virus-free by PCR for at least 6 months prior to study entry.
5. Known active or latent tuberculosis (testing at screening is not required).
9. Autoimmune disease or inflammatory condition requiring systemic therapy with
exceptions as noted in exclusion criterion 10.
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.
Pretreatment with dexamethasone is allowed for subjects receiving OR2805 in
combination with docetaxel. Inhaled, topical, or intraarticular steroids are
allowed.
11. Subject has received an investigational product or been treated with an
investigational device within 30 days prior to first administration of study
medication.
12. For Part B:
1. Known contraindication to receiving cemiplimab.
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.
13. Concurrent therapy with anti-cancer or anti-neoplastic drugs, with the exception of
adjuvant hormonal therapy, which is allowed provided the subject has undergone
potentially curative therapy with no evidence of disease for at least 3 years.
14. 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.
15. Subjects who, at the time of signing informed consent, had a recent history (within
the last year) of chronic substance abuse.
16. Subject is pregnant or breastfeeding or expecting to conceive or father children
within the projected duration of the study.
