- Analyses of non-clinical study data demonstrate longer tumor
retention with 177Lu-FAP-2286 than 177Lu-FAPI-46, resulting in
greater tumor inhibition
- Phase 1 data is expected later this year from the ongoing
LuMIERE clinical trial evaluating FAP-2286 as a therapeutic and
imaging agent in multiple solid tumors
- Non-clinical evaluation of Rubraca in tumors with mutations in
non-BRCA HRR genes showed similar efficacy to that observed in
BRCA1/2-altered models
Clovis Oncology, Inc. (NASDAQ: CLVS), announced today that two
abstracts featuring non-clinical data from studies evaluating
FAP-2286 and Rubraca and a Trial-in-Progress poster detailing the
Phase 1 portion of the LuMIERE study will be presented at the
upcoming American Association for Cancer Research (AACR) Annual
Meeting 2022, being held April 8-13, 2022, in New Orleans.
In a new non-clinical data analysis, FAP-2286 demonstrated
potent affinity for human fibroblast activation protein (FAP) by
biochemical and cell-based assays. Additionally, lutetium-177
(177Lu)-FAP-2286 showed longer tumor retention, resulting in
greater tumor inhibition as compared to lutetium-177
(177Lu)-FAPI-46, a FAP-targeted radiotracer developed for
therapeutic applications at the University of Heidelberg,
Germany.
FAP-2286 is the first peptide-targeted radionuclide therapy
(PTRT) and imaging agent targeting FAP to enter clinical
development and the lead candidate in Clovis Oncology’s targeted
radionuclide therapy (TRT) development program.
Approximately 50 patients will be enrolled in the Phase 1
portion of the multicenter, open-label LuMIERE trial, which is
currently enrolling patients with advanced solid tumors
(NCT04939610). The Phase 1 portion of the study is evaluating the
safety of the investigational therapeutic agent 177Lu-FAP-2286 and
will identify the recommended Phase 2 dose and schedule. The safety
and tumor uptake of the imaging agent gallium-68 (68Ga)-FAP-2286 is
also being evaluated. Once the Phase 2 therapeutic dose is
determined, Phase 2 expansion cohorts in multiple tumor types are
planned for later in 2022.
Separately, non-clinical data evaluating Rubraca efficacy in a
panel of tumors with deleterious alterations in a core group of
non-BRCA HRR genes showed responses similar to the efficacy
observed in BRCA1/2-altered models. The goal of the studies was to
investigate the in vitro and in vivo synthetic lethality activity
of Rubraca in multiple cancer cell types and tumors harboring
genetic or epigenetic alterations in non-BRCA HRR genes.
“The non-clinical data presented at AACR further show the
potential of FAP-2286, our first targeted radiotherapy candidate,
as a therapeutic and imaging agent and we look forward to sharing
initial clinical data from the Phase 1 portion of the LuMIERE study
of FAP-2286 later this year,” said Patrick J. Mahaffy, President
and CEO of Clovis Oncology. “We also remain committed to a greater
understanding how patients with tumors associated with different
genetic alterations may benefit from treatment with Rubraca.”
The following Clovis-sponsored posters and supplemental
information will be available as of Friday, April 8 at 1:00 p.m.
CDT at
https://clovisoncology.com/pipeline/scientific-presentations/.
FAP-2286
Abstract #3317: Comparative biodistribution and radiotherapeutic
efficacy of the fibroblast activation protein (FAP)-targeting
agents FAP-2286 and FAPI-46
- Lead Author: Dirk Zboralski, Ph.D., 3B Pharmaceuticals GmbH,
Berlin, Germany
- Poster Session: Preclinical Radiotherapeutics
- Date/Time: April 12, 1:30 – 5:00 p.m. CDT
- Key Takeaways: FAP-2286 demonstrated potent affinity for human
FAP by biochemical and cell-based assays. 177Lu-FAP-2286 showed
longer tumor retention, resulting in greater tumor inhibition as
compared to 177Lu-FAPI-46. The prolonged tumor retention of
FAP-2286 correlated with a higher intracellular accumulation.
Abstract #CT251: LuMIERE: A phase 1/2 study investigating
safety, pharmacokinetics, dosimetry, and preliminary antitumor
activity of 177Lu-FAP-2286 in patients with advanced or metastatic
solid tumors
- Lead Author: Jonathan McConathy, M.D., Ph.D., University of
Alabama School of Medicine, Birmingham, AL.
- Poster Session: Phase I Trials in Progress 2
- Date/Time: April 13, 9:00 a.m. – 12:30 p.m. CDT
- Key Takeaways: Peptide-targeted radionuclide therapy directed
toward FAP with the agent FAP-2286 has demonstrated antitumor
activity in preclinical studies. LuMIERE (NCT04939610) is an
ongoing phase 1/2, multicenter, open-label study evaluating safety
and tolerability, pharmacokinetics (PK), dosimetry, and preliminary
activity of the therapeutic agent 177Lu-FAP-2286 in patients with a
FAP-expressing solid tumor. Safety and tumor uptake of the imaging
agent 68Ga-FAP-2286 are also being evaluated.
For more information about FAP-2286, Targeted Radionuclide
Therapy (TRT), or Clovis’ TRT development program, click here.
Rubraca
Abstract #1260: Nonclinical evaluation of rucaparib in tumors
with mutations in non-BRCA1/2 homologous recombination repair (HRR)
genes
- Lead Author: Liliane Robillard, M.S., Clovis Oncology, Inc.,
Boulder, CO.
- Poster Session: Biomarkers Predictive of Therapeutic Benefit
2
- Date/Time: April 11, 9:00 a.m. – 12:30 p.m. CDT
- Key Takeaways: In vitro small interfering ribonucleic acid
(siRNA) knockdown of a subset of HRR genes showed synthetic
lethality with rucaparib treatment in ovarian and prostate cancer
cell lines. Rucaparib efficacy observed in patient-derived tumor
xenograft (PDX) models with deleterious alterations in a core group
of non-BRCA HRR genes was similar to the efficacy observed in
BRCA1/2-altered models across different solid tumors, with enhanced
sensitivity in tumors with biallelic alterations.
About FAP-2286
FAP-2286 is a clinical candidate under investigation as a
peptide-targeted radionuclide therapy (PTRT) and imaging agent
targeting fibroblast activation protein (FAP). FAP-2286 consists of
two functional elements; a targeting peptide that binds to FAP and
a site that can be used to attach radioactive isotopes for imaging
and therapeutic use. High FAP expression has been shown in
pancreatic ductal adenocarcinoma, salivary gland, mesothelioma,
colon, bladder, sarcoma, squamous non–small cell lung, squamous
head and neck cancers, and cancer of unknown primary. High FAP
expression was detected in both primary and metastatic tumor
samples and was independent of tumor stage or grade. Clovis holds
US and global rights for FAP-2286 excluding Europe, Russia, Turkey,
and Israel.
FAP-2286 is an unlicensed medical product.
About Targeted Radionuclide Therapy
Targeted radionuclide therapy is an emerging class of cancer
therapeutics, which seeks to deliver radiation directly to the
tumor while minimizing delivery of radiation to normal tissue.
Targeted radionuclides are created by linking radioactive isotopes,
also known as radionuclides, to targeting molecules (e.g.,
peptides, antibodies, small molecules) that can bind specifically
to tumor cells or other cells in the tumor environment. Based on
the radioactive isotope selected, the resulting agent can be used
to image and/or treat certain types of cancer. Agents that can be
adapted for both therapeutic and imaging use are known as
“theranostics.” Clovis, together with licensing partner 3B
Pharmaceuticals, is developing a pipeline of novel, targeted
radiotherapies for cancer treatment and imaging, including its lead
candidate, FAP-2286, an investigational peptide-targeted
radionuclide therapeutic (PTRT) and imaging agent, as well as three
additional discovery-stage compounds.
About the LuMIERE Clinical Study
LuMIERE is a Phase 1/2 study evaluating FAP-2286 as a
peptide-targeted radionuclide therapy (PTRT) targeting fibroblast
activation protein, or FAP, in patients with advanced solid tumors.
The Phase 1 portion of the LuMIERE study is evaluating the safety
of the investigational therapeutic agent and will identify the
recommended Phase 2 dose and schedule of lutetium-177 labeled
FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68
(68Ga-FAP-2286) will be utilized as an investigational imaging
agent to identify patients with FAP-positive tumors appropriate for
treatment with the therapeutic agent. Once the Phase 2 dose is
determined, Phase 2 expansion cohorts are planned in multiple tumor
types.
About Rubraca (rucaparib)
Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2
and PARP3 being developed in multiple tumor types, including
ovarian and metastatic castration-resistant prostate cancers, as
monotherapy, and in combination with other anti-cancer agents.
Exploratory studies in other tumor types are also underway.
Rubraca is an unlicensed medical product outside of the US and
Europe
Rubraca US FDA Approved Indications
Ovarian Cancer
Rubraca is indicated for the maintenance treatment of adult
women with recurrent epithelial ovarian, fallopian tube, or primary
peritoneal cancer who are in a complete or partial response to
platinum-based chemotherapy.
Rubraca is indicated for the treatment of adult women with a
deleterious BRCA mutation (germline and/or somatic)-associated
epithelial ovarian, fallopian tube, or primary peritoneal cancer
who have been treated with two or more chemotherapies. Select
patients for therapy based on an FDA-approved companion diagnostic
for Rubraca.
Prostate Cancer
Rubraca is indicated for the treatment of adult patients with a
deleterious BRCA mutation (germline and/or somatic)-associated
metastatic castration-resistant prostate cancer (mCRPC) who have
been treated with androgen receptor-directed therapy and a
taxane-based chemotherapy. This indication is approved under
accelerated approval based on objective response rate and duration
of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
confirmatory trials.
Select Important Safety Information
Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML)
occur in patients treated with Rubraca, and are potentially fatal
adverse reactions. In 1146 treated patients, MDS/AML occurred in 20
patients (1.7%), including those in long term follow-up. Of these,
8 occurred during treatment or during the 28 day safety follow-up
(0.7%). The duration of Rubraca treatment prior to the diagnosis of
MDS/AML ranged from 1 month to approximately 53 months. The cases
were typical of secondary MDS/cancer therapy-related AML; in all
cases, patients had received previous platinum-containing regimens
and/or other DNA damaging agents.
Do not start Rubraca until patients have recovered from
hematological toxicity caused by previous chemotherapy (≤ Grade 1).
Monitor complete blood counts for cytopenia at baseline and monthly
thereafter for clinically significant changes during treatment. For
prolonged hematological toxicities (> 4 weeks), interrupt
Rubraca or reduce dose and monitor blood counts weekly until
recovery. If the levels have not recovered to Grade 1 or less after
4 weeks or if MDS/AML is suspected, refer the patient to a
hematologist for further investigations, including bone marrow
analysis and blood sample for cytogenetics. If MDS/AML is
confirmed, discontinue Rubraca.
Based on its mechanism of action and findings from animal
studies, Rubraca can cause fetal harm when administered to a
pregnant woman. Apprise pregnant women of the potential risk to a
fetus. Advise females of reproductive potential to use effective
contraception during treatment and for 6 months following the last
dose of Rubraca. For males on Rubraca treatment who have female
partners of reproductive potential or who are pregnant, effective
contraception should be used during treatment and for 3 months
following the last dose of Rubraca.
Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1-4) were
nausea (76%), fatigue/asthenia (73%), abdominal pain/distention
(46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation
(38%), constipation (37%), vomiting (37%), diarrhea (32%),
thrombocytopenia (29%), nasopharyngitis/upper respiratory tract
infection (29%), stomatitis (28%), decreased appetite (23%), and
neutropenia (20%).
Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%;
Grade 1-4) were nausea (77%), asthenia/fatigue (77%), vomiting
(46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased
appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea
(21%), and thrombocytopenia (21%).
Co-administration of rucaparib can increase the systemic
exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may
increase the risk of toxicities of these drugs. Adjust dosage of
CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically
indicated. If co-administration with warfarin (a CYP2C9 substrate)
cannot be avoided, consider increasing frequency of international
normalized ratio (INR) monitoring.
Because of the potential for serious adverse reactions in
breast-fed children from Rubraca, advise lactating women not to
breastfeed during treatment with Rubraca and for 2 weeks after the
last dose.
Please Click here for full Prescribing Information for
Rubraca.
You may also report side effects to Clovis Oncology, Inc. at
1-415-409-7220 (US toll) or 1-844-CLVS-ONC (1-844-258-7662; US
toll-free).
About Clovis Oncology
Clovis Oncology, Inc. is a biopharmaceutical company focused on
acquiring, developing, and commercializing innovative anti-cancer
agents in the US, Europe, and additional international markets.
Clovis Oncology targets development programs at specific subsets of
cancer populations, and simultaneously develops, with partners, for
those indications that require them, diagnostic tools intended to
direct a compound in development to the population that is most
likely to benefit from its use. Clovis Oncology is headquartered in
Boulder, Colorado, with additional office locations in the US and
Europe. Please visit www.clovisoncology.com for more
information.
To the extent that statements contained in this press release
are not descriptions of historical facts regarding Clovis Oncology,
they are forward-looking statements reflecting the current beliefs
and expectations of management made pursuant to the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
Examples of forward-looking statements contained in this press
release include, among others, statements of our intentions and
expectations for our development and discovery programs, including
the timing and pace of pre-clinical development, plans for and
expected timing and pace of clinical development, plans for
additional applications of Rubraca and the FAP-2286 peptide,
including potential indications, tumor types and combination
trials, plans for presentation of data and regulatory plans with
respect to Rubraca FAP-2286. Such forward-looking statements
involve substantial risks and uncertainties that could cause Clovis
Oncology’s actual results, performance or achievements to differ
significantly from those expressed or implied by the
forward-looking statements. Such risks and uncertainties include,
among others, the uncertainties inherent in drug discovery and
pre-clinical and clinical development, including the outcome of
pre-clinical studies and clinical trials, whether initial results,
findings or research will support future studies or development,
whether future study results will be consistent with previous study
findings or other results, including pre-clinical studies, results
in named-patient or similar programs or clinical trials, whether
additional studies not originally contemplated are determined to be
necessary, the timing of initiation, enrollment and completion of
planned studies and actions by the FDA, the EMA or other regulatory
authorities regarding data required to support drug applications
and whether to approve drug applications. Clovis Oncology
undertakes no obligation to update or revise any forward-looking
statements. For a further description of the risks and
uncertainties that could cause actual results to differ from those
expressed in these forward-looking statements, as well as risks
relating to the business of the company in general, see Clovis
Oncology’s Annual Report on Form 10-K, Quarterly Reports on Form
10-Q and its other reports filed with the Securities and Exchange
Commission.
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version on businesswire.com: https://www.businesswire.com/news/home/20220408005046/en/
Clovis Investor Contacts: Anna Sussman, 303.625.5022
asussman@clovisoncology.com or Breanna Burkart, 303.625.5023
bburkart@clovisoncology.com
Clovis Media Contacts: US Lisa Guiterman,
301.347.7964 clovismedia@clovisoncology.com
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