Trial Title:
A Study to Learn About the Study Medicine PF-07934040 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Genetic Mutation.
NCT ID:
NCT06447662
Condition:
Carcinoma, Pancreatic Ductal
Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Conditions: Official terms:
Carcinoma
Neoplasms
Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Pancreatic Ductal
Calcium, Dietary
Leucovorin
Paclitaxel
Albumin-Bound Paclitaxel
Bevacizumab
Carboplatin
Gemcitabine
Pembrolizumab
Oxaliplatin
Fluorouracil
Pemetrexed
Cetuximab
Calcium
Levoleucovorin
Conditions: Keywords:
Carcinoma, Pancreatic Ductal
Carcinoma, Ductal, Pancreatic
Duct-Cell Carcinoma of the Pancreas
Duct-Cell Carcinoma, Pancreas
Ductal Carcinoma of the Pancreas
Pancreatic Duct Cell Carcinoma
Pancreatic Ductal Carcinoma
pancreatic ductal adenocarcinoma
PADC
Colorectal Neoplasms
Colorectal Cancer
Colorectal Carcinoma
Colorectal Tumors
Neoplasms, Colorectal
Rectal Cancer
Colon Cancer
CRC
MSS CRC
Carcinoma, Non-Small-Cell Lung
Non-Small Cell Lung Cancer
Non-Small Cell Lung Carcinoma
Non-Small-Cell Lung Carcinoma
Nonsmall Cell Lung Cancer
Lung Cancer
NSCLC
KRAS
KRAS gene mutation
G12C
G12D
G12V
G12R
G12S
G13D
Q61H
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PF-07934040
Description:
panKRAS inhibitor
Arm group label:
Part 1
Arm group label:
Part 2a Cohort A1
Arm group label:
Part 2a Cohort B1
Arm group label:
Part 2a Cohort C1
Arm group label:
Part 2b Cohort A2
Arm group label:
Part 2b Cohort B2
Arm group label:
Part 2b Cohort B3
Arm group label:
Part 2b Cohort C2
Arm group label:
Part 2b Cohort C3
Other name:
PF-4040
Intervention type:
Combination Product
Intervention name:
Gemcitabine
Description:
Chemotherapy (antimetabolite)
Arm group label:
Part 2b Cohort A2
Other name:
Gemzar
Intervention type:
Combination Product
Intervention name:
Nab-paclitaxel
Description:
Taxane-type Chemotherapy
Arm group label:
Part 2b Cohort A2
Other name:
Abraxane
Intervention type:
Combination Product
Intervention name:
Cetuximab
Description:
Monoclonal Antibody (EGFR Inhibitor)
Arm group label:
Part 2b Cohort B2
Other name:
Erbitux
Intervention type:
Combination Product
Intervention name:
Fluorouracil
Description:
Part of FOLFOX chemotherapy regimen
cytotoxic chemotherapy (antimetabolite and pyrimidine analog)
Arm group label:
Part 2b Cohort B3
Other name:
5-FU
Other name:
5-fluorouracil
Intervention type:
Combination Product
Intervention name:
Oxaliplatin
Description:
Part of FOLFOX Chemotherapy Regimen
platinum based compound (alkylating agent)
Arm group label:
Part 2b Cohort B3
Other name:
Eloxatin
Intervention type:
Combination Product
Intervention name:
Leucovorin
Description:
Part of FOLFOX chemotherapy regimen
Folic Acid Analog
Arm group label:
Part 2b Cohort B3
Other name:
Folinic Acid
Other name:
Wellcovorin
Other name:
calcium folinate
Other name:
Leucovorin Calcium
Intervention type:
Combination Product
Intervention name:
Bevacizumab
Description:
VEG-F inhibitor
Arm group label:
Part 2b Cohort B3
Other name:
Zirabev
Other name:
Avastin
Intervention type:
Combination Product
Intervention name:
Pembrolizumab
Description:
immune checkpoint inhibitor (PD-1 inhibitor)
Arm group label:
Part 2b Cohort C2
Arm group label:
Part 2b Cohort C3
Other name:
Pembro
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
Keytruda
Intervention type:
Combination Product
Intervention name:
pemetrexed
Description:
Can be used in Platinum-based Chemotherapy regimen
Antimetabolite
Arm group label:
Part 2b Cohort C3
Other name:
Alimta
Intervention type:
Combination Product
Intervention name:
Cisplatin
Description:
Can be used as part of Platinum-based chemotherapy regimen
Platinum-based antineoplastic (alkylating agent)
Arm group label:
Part 2b Cohort C3
Other name:
Platinol
Other name:
Cisplatinum
Other name:
neoplatin
Intervention type:
Combination Product
Intervention name:
Paclitaxel
Description:
Can be used in Platinum-based chemotherapy regimen
Taxane
Arm group label:
Part 2b Cohort C3
Other name:
Taxol
Other name:
Onxol
Intervention type:
Combination Product
Intervention name:
Carboplatin
Description:
Can be used as part of a platinum-based chemotherapy regimen
platinum containing compound (alkylating agent)
Arm group label:
Part 2b Cohort C3
Other name:
Paraplatin
Other name:
Stricarb
Summary:
The purpose of this study is to learn about the safety and effects of the study medicine
alone or when given together with other anti-cancer therapies. This study also aims to
find the best dose.
This study is seeking participants who have solid tumors (a mass of abnormal cells that
forms a lump or growth in the body) that:
- are advanced (cancer that doesn't disappear or stay away with treatment) and
- have a KRAS gene mutation (a change in the DNA of the KRAS gene that can cause cells
to grow in very high numbers).
This includes (but limited to) the following cancer types:
Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow
slowly but often spread to other parts of the body.
Colorectal Cancer (CRC): This is a disease where cells in the colon (a part of large
intestine) or rectum grow out of control.
Pancreatic ductal adenocarcinoma (PDAC): This is a cancer that starts in the ducts of the
pancreas but can spread quickly to other parts of the body. Pancreas is a long, flat
gland that lies in the abdomen behind the stomach. Pancreas creates enzymes that help
with digestion. It also makes hormones that can help control your blood sugar levels.
All participants in this study will take the study medication (PF-07934040) as pill by
mouth twice a day repeating for 21-day or 28-day cycles.
Depending on which part of the study participants are enrolled into they will receive the
study medication (PF-07934040 alone or in combination with other anti-cancer
medications). These anti-cancer medications will be given in the study clinic by
intravenous (IV) that is directly injected into the veins at various times (depending on
the treatment) during the 21-day or 28-day cycle.
Participants can continue to take the study medication (PF-07934040) and the combination
anti-cancer therapy until their cancer is no longer responding.
The study will look at the experiences of people receiving the study medicines. This will
help see if the study medicines are safe and effective.
Participants will be involved in this study for up to 4 years. During this time, they
will come into the clinic between 1 to 4 times in each 21-day or 28-day cycle. After they
have stopped taking the study medication (at about at 2 years) they will be followed for
another two years to see how they are doing.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histological or cytological diagnosis of advanced, unresectable, and/or metastatic
or relapsed/refractory solid tumor.
ECOG PS 0 or 1
- Presence of at least 1 measurable lesion based on RECIST version 1.1 that has not
been previously irradiated.
- Documentation of mutated KRAS gene
1. PDAC, CRC, Other tumor types: Confirmed KRAS mutation, any variant
2. NSCLC: Confirmed KRAS mutation, any variant except previously treated G12C. If
driver mutation, must have failed precision medicine therapy [eg, inhibitors of
epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK),
c-ros oncogene 1 (ROS1), and others].
- Part 1 and Part 2a: Participant must have progressed on standard treatment(s) for
which no additional, effective therapy is available.
1. PDAC (2-3L): Participants must have received and radiologically progressed on
prior lines of systemic therapy for metastatic pancreatic adenocarcinoma. If
participants received prior neoadjuvant or adjuvant chemotherapy and progressed
within 6 months of the last dose, then this should be considered as a prior
line of systemic therapy.
2. NSCLC (2-3L): Participants must have received prior lines of anti-cancer
treatment and progressed on at least a platinum-containing chemotherapy regimen
and checkpoint inhibitor therapy; for participants with EGFR, ALK, or other
genomic tumor alterations, participants must have progressed on approved
therapy for these alterations.
3. CRC (2-3L): Participants must have had one or two prior systemic treatment
regimens for mCRC. For either one or two prior treatments, these regimens must
have included a fluoropyrimidine, oxaliplatin, or irinotecan; for one prior
treatment, exposure to VEGF/VEGF receptor (VEGFR) inhibitor is optional;
4. Other tumors: Participants, in the judgment of the investigator, must have
progressed or become intolerant to all available standard therapies, or have
refused such therapy.
- Part 2b:
1. PDAC (1L) Cohort A2: Participants must not have received prior chemotherapy for
metastatic disease. Participant could have received neoadjuvant therapy,
adjuvant therapy, or adjuvant chemo-radiotherapy, as long as relapse did not
occur within 6 months of completing these forms of adjuvant treatment. If so,
the relapse within 6 months would be considered a line of therapy; the
participant would be considered 2L, and not 1L.
2. CRC (2-3L) Cohort B2: Participants must have had one or two prior systemic
treatment regimens for mCRC. For either one or two prior treatments, these
regimens must have included a fluoropyrimidine, irinotecan, oxaliplatin; for
one prior treatment, exposure to a VEGF/VEGF receptor (VEGFR) inhibitor is
optional.
3. CRC (1L) Cohort B3: Participants must not have had prior chemotherapy for
advanced or metastatic disease. Participant could have received adjuvant
chemotherapy or adjuvant chemo-radiotherapy, as long as relapse did not occur
within 6 months of complete of adjuvant therapy. If so, the relapse within 6
months would be considered a line of therapy; the participant would be
considered 2L, and not 1L.
4. NSCLC (1L) Cohort C2: Participants must have a TPS ≥50% and must not have
received prior systemic treatment setting.
5. NSCLC (1L) Cohort C3: Participants with any TPS and must not have received
prior systemic treatment setting.
Exclusion Criteria:
- Active or history of pneumonitis/ILD, pulmonary fibrosis requiring treatment with
systemic steroid therapy, including evidence to suggest pneumonitis/ILD on baseline
assessments including imaging.
- Diagnosis of immunodeficiency or an active autoimmune disease that require systemic
treatment with chronic systemic steroid therapy (in dosing exceeding 10 mg daily of
prednisone equivalent) or any other form of immunosuppressive therapy in the past 2
years.
- Sensory peripheral neuropathy ≥Grade 2
- Active or history of clinically significant gastrointestinal (GI) disease (including
but not limited to inflammatory GI disease [eg, ulcerative colitis, Crohn's disease,
inflammatory bowel disease], immune-mediated colitis, peptic ulcer disease, GI
bleeding, chronic diarrhea) and other conditions that are unresolved and/or may
increase the risk associated with study participation or study treatment
administration.
- Active bleeding disorder, including GI bleeding, as evidenced by hematemesis,
significant hemoptysis or melena in the past 6 months.
- Major surgery or completion of radiation therapy ≤4 weeks prior to
enrollment/randomization or radiation therapy that included >30% of the bone marrow.
- Known sensitivity or contraindication to any component of study intervention (PF
07934040, gemcitabine, nab-paclitaxel, cetuximab, bevacizumab, FOLFOX, 5-FU,
pembrolizumab, cisplatin, carboplatin, pemetrexed, SHP2 inhibitor(s),
cyclin-dependent kinase (CDK) inhibitor(s), antibody drug conjugates (ADCs) or EGFR
inhibitor(s)).
- Hematologic abnormalities.
- Renal impairment.
- Hepatic abnormalities.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Highlands Oncology Group, PA
Address:
City:
Fayetteville
Zip:
72703
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Highlands Oncology Group, PA
Address:
City:
Rogers
Zip:
72758
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Highlands Oncology Group
Address:
City:
Springdale
Zip:
72762
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Facility:
Name:
City of Hope Investigational Drug Service (IDS)
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Facility:
Name:
START Midwest
Address:
City:
Grand Rapids
Zip:
49546
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Pan American Center for Oncology Trials, LLC
Address:
City:
Rio Piedras
Zip:
00935
Country:
Puerto Rico
Status:
Recruiting
Start date:
June 27, 2024
Completion date:
June 7, 2028
Lead sponsor:
Agency:
Pfizer
Agency class:
Industry
Source:
Pfizer
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06447662
https://pmiform.com/clinical-trial-info-request?StudyID=C5421001
