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.

• PF-07934040 (Drug), also known as PF-4040: panKRAS inhibitor
• Gemcitabine (Combination product), also known as Gemzar: Chemotherapy (antimetabolite)
• Nab-paclitaxel (Combination product), also known as Abraxane: Taxane-type Chemotherapy
• Cetuximab (Combination product), also known as Erbitux: Monoclonal Antibody (EGFR Inhibitor)
• Fluorouracil (Combination product), also known as 5-FU, 5-fluorouracil: Part of FOLFOX chemotherapy regimen cytotoxic chemotherapy (antimetabolite and pyrimidine analog)
• Oxaliplatin (Combination product), also known as Eloxatin: Part of FOLFOX Chemotherapy Regimen platinum based compound (alkylating agent)
• Leucovorin (Combination product), also known as Folinic Acid, Wellcovorin, calcium folinate, Leucovorin Calcium: Part of FOLFOX chemotherapy regimen Folic Acid Analog
• Bevacizumab (Combination product), also known as Zirabev, Avastin: VEG-F inhibitor
• Pembrolizumab (Combination product), also known as Pembro, Lambrolizumab, MK-3475, Keytruda: immune checkpoint inhibitor (PD-1 inhibitor)
• pemetrexed (Combination product), also known as Alimta: Can be used in Platinum-based Chemotherapy regimen Antimetabolite
• Cisplatin (Combination product), also known as Platinol, Cisplatinum, neoplatin: Can be used as part of Platinum-based chemotherapy regimen Platinum-based antineoplastic (alkylating agent)
• Paclitaxel (Combination product), also known as Taxol, Onxol: Can be used in Platinum-based chemotherapy regimen Taxane
• Carboplatin (Combination product), also known as Paraplatin, Stricarb: Can be used as part of a platinum-based chemotherapy regimen platinum containing compound (alkylating agent)
• Sasanlimab (Combination product), also known as PF-06081591: immune checkpoint inhibitor (PD-1 inhibitor)

Primary outcomes

• Part 1 & 2: Incidence of Adverse Events (AEs) [Start of treatment up to 30 days after last dose or start of new anticancer therapy (whichever occurs first)]: 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 [From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first]: 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) [Baseline up to 28 days]: 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) [Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years']: 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.

Secondary outcomes

• Part 1 & 2: Maximum Observed Serum Concentration (Cmax) [baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)]: 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) [Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)]: 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) [Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)]: 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 [Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)]: 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.
• Part 1: Objective Response - Number of Participants With Objective Response [Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years]: 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) assessed by the Investigator including overall response rate (ORR), progression free survival (PFS), and overall survival (OS).
• Part 1: Effect of Food on Cmax [Baseline through end of Cycle 1 (All cycles are 28 days)]: Evaluate the effect of food on Cmax of PF-07934040 as monotherapy.
• Part 1: Effect of Food on Tmax [Baseline through end of Cycle 1 (All cycles are 28 days)]: Evaluate the effect of food on Tmax of PF-07934040 as monotherapy.
• Part 1: Effect of Food on AUClast [Baseline through end of Cycle 1 (All cycles are 28 days)]: Evaluate the effect of food on AUClast of PF-07934040 as monotherapy.

Sex: All, ages: 18 Years to any

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 or ICI. Participants may have had only one or two prior lines of therapy in the advanced/metastatic setting. 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 lines of therapy for mCRC. For either one or two prior treatments, these regimens must have included a fluoropyrimidine, oxaliplatin, and/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. If relapse occurred within 6 months of last dose of adjuvant treatment or neoadjuvant 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/B4: Participants must not have received prior therapy for metastatic disease and not be a candidate for other targeted therapy or immunotherapy. Participant could have received neoadjuvant therapy, adjuvant therapy, or adjuvant chemo-radiotherapy. If relapse occurred within 6 months of last dose of adjuvant or neoadjuvant therapy, then 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 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.
* 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.

• Pfizer CT.gov Call Center, Study director, Pfizer