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.
Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor.
Presence of at least 1 measurable lesion based on RECIST version 1.1 that has not been previously irradiated.
Documentation of mutated KRAS gene
PDAC, CRC, Other tumor types: Confirmed KRAS mutation, any variant
Active or history of pneumonitis/ILD or pulmonary fibrosis requiring treatment with systemic steroid therapy.
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.
Sequential
PF-07934040
DrugpanKRAS inhibitor
Gemcitabine
Combination productChemotherapy (antimetabolite)
Nab-paclitaxel
Combination productTaxane-type Chemotherapy
Cetuximab
Combination productMonoclonal Antibody (EGFR Inhibitor)
Fluorouracil
Combination productPart of FOLFOX chemotherapy regimen cytotoxic chemotherapy (antimetabolite and pyrimidine analog)
Oxaliplatin
Combination productPart of FOLFOX Chemotherapy Regimen platinum based compound (alkylating agent)
Leucovorin
Combination productPart of FOLFOX chemotherapy regimen Folic Acid Analog
Bevacizumab
Combination productVEG-F inhibitor
Pembrolizumab
Combination productimmune checkpoint inhibitor (PD-1 inhibitor)
pemetrexed
Combination productCan be used in Platinum-based Chemotherapy regimen Antimetabolite
Cisplatin
Combination productCan be used as part of Platinum-based chemotherapy regimen Platinum-based antineoplastic (alkylating agent)
Paclitaxel
Combination productCan be used in Platinum-based chemotherapy regimen Taxane
Carboplatin
Combination productCan be used as part of a platinum-based chemotherapy regimen platinum containing compound (alkylating agent)
Sasanlimab
Combination productimmune checkpoint inhibitor (PD-1 inhibitor)
11
Treatment groupsSee each treatment group below.
Part 1 & 2: Incidence of Adverse Events (AEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.
PART 1 & 2: Number of participants with laboratory abnormalities
Number of participants with laboratory test abnormalities. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).
Part 1: Number of participants with Dose-limiting toxicities (DLT)
Any of the prespecified AEs that are attributable to one, the other, or both study treatments, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes
Part 2: Objective Response - Number of Participants With Objective Response (alone or in combination)
Percentage of participants with objective response-based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for overall response rate (ORR), progression free survival (PFS), and overall survivor (OS) assessed by the Investigator.
Part 1 & 2: Maximum Observed Serum Concentration (Cmax)
Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.
Part 1& 2: Time to Reach Maximum Observed Serum Concentration (Tmax)
Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.
Part 1 & 2: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.
Part 1 & 2: Changes in pERK levels
Evaluates the intended mechanism of action (MoA) modulation of KRAS inhibition and target engagement effect of PF-07934040 in peripheral blood of participants with advanced solid tumor malignancies.
